Homopolymers and copolymers having recurring carbonate units

ABSTRACT

This invention relates to medical devices formed totally or in part from homopolymers or copolymers comprising recurring carbonate moieties.

RELATED APPLICATIONS

This application is a division of application Ser. No. 227,386, filedAug. 2, 1988, now U.S. Pat. No. 4,920,203, which in turn is acontinuation-in-part of U.S. Ser. No. 134,290 filed Dec. 17, 1987, nowabandoned, and a continuation-in-part of U.S. Ser. No. 134,321, filedDec. 17, 1987, now U.S. Pat. No. 4,891,263, and a continuation-in-partof U.S. Ser. No. 134,339, filed Dec. 17, 1987.

FIELD OF THE INVENTION

This invention relates to totally and partially bioresorbable devicescapable of degrading into biologically innocuous components and tobiodurable medical devices suitable for contacting blood and/or livingsystems. More particularly, this invention relates to such devices whichare fabricated totally or in part from copolymers and homopolymershaving recurring carbonate moieties.

BACKGROUND OF INVENTION

Polycarbonates have been known for a number of years. U.S. Pat. No.3,301,824 describes the preparation of carbonate homopolymers and randomcopolymers with cyclic lactones. While the patent generally disclosesthe polymers as having utility in the molding, coating, fiber andplasticizing fields, there is no appreciation whatsoever ofbiodegradable and/or bioresorbable devices composed in whole or in partof polycarbonate.

Non-bioresorbable synthetic permanent vascular grafts have beenavailable and are made of either Dacron (polyethylene terephthalate) ormicroporous Teflon (polytetrafluoroethylene). Various prostheses such asgrafts, and especially those of small diameters for use in coronarybypass procedures, must have certain properties. These propertiesinclude physical and mechanical compatibility with the vessel to whichthey are connected, suturability, compliancy, ability to withstandpressure and pressure fluctuations, and flexibility. Required propertiesalso include biocompatibility, sterilizability, and low toxicity,allergenicity, and mutagenicity. Still other required properties includedurability, both in terms of "shelf life" after fabrication andappropriate durability after implantation. Problems which arise from amismatch of a native vessel and a prosthesis include dilation which mayresult in aneurysm formation and anastomotic hyperplasia, kinking andthe like. Vascular grafts having internal diameters of 8 mm or more andmade of biodurable materials have so far been the only successfulprostheses for providing a conduit for maintaining continuous blood flowwhile inflicting a minimal hematologic trauma. Vascular grafts made ofDacron in current clinical use are constructed of knitted or wovenDacron fibers with open pores in the fabric which have to be closed ordiminished by preclotting before implantation. Such prostheses have beenused as vascular replacements, but only for the relatively largerarteries.

Bioresorbable polymers have been used in the fabrication of devices forimplantation in living tissue for several decades. Medical applicationof such polymers include absorbable sutures, haemostatic aids and,recently, intraosseous implants and control-release drug deliverysystems, to name but a few. Use of such polymers has been extended totissue regeneration devices such as nerve channels, vascular grafts,sperm duct channels, fallopian tube ducts or channels and the like. Tobe effective, these devices must be made from materials that meet a widerange of biological, physical and chemical prerequisites. The materialmust be bioresorbable at least in part, nontoxic, noncarcinogenic,nonantigenic, and must demonstrate favorable mechanical properties suchas flexibility, suturability in some cases, and amenability to customfabrication.

Various polymers have been proposed for use in the fabrication ofbioresorbable medical devices. Examples of absorbable materials used innerve repair include collagen as disclosed by D. G. Kline and G. J.Hayes, "The Use of a Resorbable Wrapper for Peripheral Nerve Repair,Experimental Studies in Chimpanzees", J. Neurosurgery 21, 737 (1964).Artandi et al., U.S. Pat. No. 3,272,204 (1966) reports the use ofcollagen protheses that are reinforced with nonabsorbable fabrics. Thesearticles are intended to be placed permanently in a human body. However,one of the disadvantages inherent with collagenous materials, whetherutilized alone or in conjunction with biodurable materials, is theirpotential antigenicity.

U.S. Pat. Nos. 4,033,938 and 3,960,152 disclose bioabsorbable polymersof unsymmetrically substituted 1,4-dioxane-2,5-diones which the patentbroadly states are useful as tubes or sheets for surgical repair such asnerve and tendon splicing. A similar disclosure is in U.S. Pat. No.4,074,366 relates to poly(N-acetyl-D-glucosamine), i.e., chitin.

Other biodegradable polymers of particular interest for medicalimplantation purposes are homopolymers and copolymers of glycolic acidand lactic acid. A nerve cuff in the form of a smooth, rigid tube hasbeen fabricated from a copolymer of lactic and glycolic acids [The Hand;10 (3) 259 (1978)]. European patent application 118-458-A disclosesbiodegradable materials used in organ protheses or artificial skin basedon poly-L-lactic acid and/or poly-DL-lactic acid and polyester orpolyether urethanes.

U.S. Pat. No. 4,481,353 discloses bioresorbable polyester polymers, andcomposites containing these polymers, that are also made up ofalpha-hydroxy carboxylic acids, in conjunction with Krebs cycledicarboxylic acids and aliphatic diols. These polyesters are useful infabricating nerve guidance channels as well as other surgical articlessuch as sutures and ligatures.

U.S. Pat. Nos. 4,243,775 (1981) and 4,429,080 (1984) disclose the use ofpolycarbonate-containing polymers in certain medical applications,especially sutures, ligatures and haemostatic devices. However, thisdisclosure is clearly limited only to "AB" and "ABA" type blockcopolymers where only the "B" block contains poly(trimethylenecarbonate) or a random copolymer of glycolide with trimethylenecarbonate and the "A" block is necessarily limited to glycolide. In thecopolymers of this patent, the dominant portion of the polymer is theglycolide component.

SUMMARY OF THE INVENTION

The present invention relates to a bioresorbable or biodurable medicaldevice fabricated totally or in part from a biopolymer selected from thegroup consisting of homopolymers or copolymers having at least one typeof recurring monomeric unit of the Structures I and II: ##STR1##wherein:

Z is --C(R₅ R₆)--, --NR₅ --, --O-- or a combination thereof, where Z isselected such that there are no adjacent heteroatoms;

n is from 1 to about 8;

m is from 1 to about 8;

R₁, R₂, R₃, and R₄ are the same or different at each occurrence and arehydrogen, aryloxyalkyl, alkoxyaryl, aryloxyaryl, arylalkyl,alkylarylalkyl, arylalkylaryl, alkylaryl, arylcarbonylalkyl, alkyl,aryl, alkylcarbonylalkyl, cycloalkyl, arylcarbonylaryl,alkylcarbonylaryl, alkoxyalkyl, or aryl or alkyl substituted with one ormore biologically compatible substituents such as alkyl, aryl, alkoxy,aryloxy, dialkylamino, diarylamino, alkylarylamino substituents;

R₅ and R₆ are the same or different at each occurrence and are R₁, R₂,R₃, R₄, dialkylamino, diarylamino, alkylarylamino, alkoxy, aryloxy,alkanoyl, or arylcarbonyl; or

any two of R₁ to R₆ together can form an alkylene chain completing a 3,4, 5, 6, 7, 8 or 9 membered alicyclic, fused, spiro, bicyclic and/ortricyclic ring system, which system may optionally include one or morenon-adjacent carbonyl, oxa, alkylaza, or arylaza groups; with theproviso that when said biopolymer is a copolymer having recurringmonomeric units of the Structure I derived from trimethylene carbonate,the other recurring monomeric units of said copolymer are not derivedfrom glycolide or glycolic acid and with the proviso that when saidbiopolymer is a homopolymer having recurring monomeric units of theStructure II derived from ethylene carbonate and propylene carbonate, mis other than 1.

The biopolymers used in the practice of this invention exhibit variousphysical and morphological properties which enable their use in thefabrication of a large number of medical devices. For example, thebiopolymers used in the practice of this invention may be crystalline tosemi-crystalline to amorphous, having varying modulus and tensilestrength. Certain biopolymers of this invention which exhibit highmodulus, high tensile strength and relatively slow rates ofbioresorbabilities which can be conveniently processed to form highstrength medical devices and fibers of various deniers where highstrength and slow rates of bioresorbabilities are critical to theefficacy of the device. The device may be implanted in humans to aid intissue regeneration, growth and/or healing, or may be used outside ofthe body but in contact with living tissue, body fluids and/or bloodwithout undue adverse impact on such tissue, fluids and/or blood. Otherbiopolymers used in the practice of this invention are amorphous, softand pliable materials having relatively fast rates of bioresorbabilitywhich can be fabricated into solid medical devices, thin films, coatingsand the like where softness and pliability are necessary requirementsfor the efficacy of the device. Yet other biopolymers used in thisinvention are strong, elastic and pliable materials having intermediateor slower rates of bioresorbability which can be fabricated into devicessuch as nerve channels, vascular graft body, sutures, tendon or ligamentreplacements and the like, where elasticity, strength, pliability and anintermediate or slow rate of bioresorbability are necessary requirementsfor efficacy of the device. Still other biopolymers used in thisinvention are elastomeric which allow their use in the fabrication ofelastic fibers and medical devices, coatings, films and the like wherecertain elasticity is critical for efficacy.

The biopolymers for use in the fabrication of the device of thisinvention exhibit controllable bioresorbability and biodegradationrates, blood compatability, and biocompatibility with living tissue.These biopolymers also induce minimal inflammatory tissue reaction. Thebiodegradation of the biopolymers used to fabricate the biodegradabledevices of this invention usually results in degradation products havinga physiologically neutral or relatively neutral pH. Various propertiesof the biopolymers used in the practice of this invention render devicesmade from the biopolymers especially suitable for medical applicationsincluding but not limited to fabrication of the bioresorbable andbiodurable medical devices, such as vascular grafts, stents, fallopiantubes, sperm ducts, wound and skin covers, sutures, hemostatic aids,materials for tendon or ligament repair, bone or dental repair, tubingand parts which are intended to contact the blood, fluids and/or tissueof a living system, e.g., tubings and parts for use in an extracorporealloop, and biodurable tubings and parts implantable into a living system.

As used herein, "living system" is a living cell, animal or plant,whatever phylogenetic level in the plant or animal kingdom.

As used herein, "biologically innocuous components" are components whichmay be contacted or implanted into living systems without inducing anadverse reaction and/or components which may be metabolized by theliving systems.

As used herein, the term "biodegradable" means capable of being brokendown into products by a living system.

As used herein, "homopolymer" is a polymer having the same repeatingmonomeric unit throughout its structure, which unit is of the StructureI of II as described above.

As used herein, "copolymer" is a polymer having at least two dissimilarrepeating monomeric units throughout its structure which are distributedrandomly or in a block fashion at least one of which is of the StructureI or II.

As used herein, "medical device" is a device used within or without ahuman body or animal body to achieve certain medical benefits or goals.

As used herein, "bioresorbable" is capable of being broken down andmetabolized by a living system.

As used herein, the term "biopolymer" is a hemopolymer and/or copolymercollectively.

As used herein, "biocompatible" is the capability to exist or coexistinside or in close contact with the living systems without adverselyimpacting the system.

As used herein, "biodurable" means that the device is substantially notbiodegradable or bioresorbable.

DETAILED DESCRIPTION OF THE INVENTION

This invention is directed to medical devices. The medical devices ofthis invention may be biodurable, or may be totally or partiallybioresorbable and/or biodegradable. The devices of the invention arefabricated totally or in part of at least one biopolymer of thisinvention or a combination thereof. The biopolymers may be used tofabricate the total device, or may be use to fabricate only a part ofthe device, for example, as a coating or a layer or in a mixture withother materials. The only requirement is that the device is fabricatedwholly or partially from at least one biopolymer comprising at least onetype of recurring monomeric unit of the General Structure I or II.

The devices of this invention can be fabricated into solid articlesusing conventional techniques for fabricating parts from thermoplasticpolymers such as injection molding, melt extrusion, solution extrusion,gel extrusion and the like. Fibrous devices of this invention can befabricated from the fibers of this invention using conventionaltechniques for forming woven, knitted or like articles from fibers madeof synthetic polymers, and the fibers in turn can be formed usingconventional fiber-forming techniques such as melt spinning, gelspinning, solution spinning, dry spinning and the like. Theseconventional procedures are well known in the art and will not bedescribed herein in any great detail.

The device of this invention may take many forms and have varyingdegrees of bioresorbability and/or biodegradability, depending onintended use. For example, the devices of this invention may be solidarticles, or may be fibrous constructed of woven or non-woven fabricmade of fibers formed from the biopolymers of this invention or may becombination of solid and fibrous portions. For example, the device ofthis invention may be fabricated from fibers and/or yarns which havebeen woven, braided and/or knitted into fabrics having variousstructural configurations using conventional means, which fabrics maythen be used to fabricate a device, such as a wound cover, gauze, and avascular graft. The device may be a solid part which has been fabricatedinto the desired shape using a conventional technique for fabricatingparts out of thermoplastics, such as extrusion, molding and solutioncasting, such as an extruded hollow tubular nerve channel or extrudedhollow vascular graft, or a stent for use in angioplasty. The device mayalso be a composite device having a body which is composed of a wovenfabric or a solid part which may or may not be formed from one or morebiopolymers of this invention coated with one or more biopolymers ofthis invention using such techniques as moldings, solution dipping andsolution coating; or the device may be a layered device in which one ormore layers are formed from the biopolymers of this invention.Illustrative of useful devices of this invention are orthopedic andfracture fixation devices such as maxillo facial repair inplants,intraosseous implants, pins, clamps, screws and plates; vascularimplants such as vascular grafts; wound closing device such a sutures,fasteners, clips and staples; nerve channels; vascular stents; and thelike. Illustrative or still other devices within the scope of thisinvention are devices for tendon and ligament replacement, breastprostheses, wound and burn covering, dental repair, sponges, tracheolarreplacements, hernia patches, absorbant swabs, fallopian tube and spermducts, drug delivery devices and the like.

The rate of bioresorption and/or biodegradation exhibited by the deviceof this invention will vary depending on the desired longevity of thedevice. For example, because of the relatively high degree ofcompatibility between the biopolymers used in the construction of thedevice of this invention and blood and tissue of living systems, onedevice of this invention is a conventional part which contacts blood orliving tissue such as tubing of an extracorporeal loop or other types offlow-through systems for blood, heart valves and the like. In suchinstances, the device should be formed or at least have a surface whichwill contact the blood and/or the living tissue coated with a biopolymerhaving a relatively slow rate of bioresorbability and/orbiodegradeability or which is even relatively biodurable. On the otherhand, another device of this invention is a vascular graft composed of afabric composed of a relatively biodurable material such as Dacron or abioresorbable biopolymer having a relatively slow rate of bioresorptioncoated with a relatively fast bioresorbing biopolymer, especially in theinside of the graft. The use of the coating having fast rate ofbioresorption provides for a regenerated blood vessel having a highdegree of patency and relatively low rate of thrombosis.

In one preferred embodiment of this invention, the devices are composedof solid articles which are fabricated from the biopolymers through useof conventional techniques such as injection molding, gel or meltextrusion and the like for fabricating solid articles from thermoplasticpolymers. These techniques are well known in the art and will not bedescribed herein in any great detail. For example, such techniques aredescribed in Encyclopedia of Polymer Science and Technology,InterScience, New York. The preferred solid devices of this inventionare relatively biodurable tubing and coatings which will contact theblood or tissue of a living system, biresorbable and/or biodegradableorthopedic pins and plates, extruded wound and burn coverings, extrudednerve growth channels, extruded fibers for use in tendon and ligamentrepair.

In another preferred embodiment of the invention, the devices arefibrous devices fabricated totally from fibers composed of thebiopolymers of this invention. The fibers, which are also devices ofthis invention, are prepared by any suitable fiber-forming technique,and the fibers can then be fabricated into useful medical devices usingconventional techniques. For example, fibers made of the biopolymers maybe formed by conventional processes such as spinning techniques,including melt, solution, dry and gel spinning. Illustrative of suitablefiber spinning processes and melt spinning techniques and apparatus forcarrying out these processes are those described in "Man Made FibersScience and Technology", vol. 1-3, H. F. Mark et al., Interscience, NewYork, 1968; "Encyclopedia of Polymer Science and Technology", Vol 3;Fundamentals of Fiber Formation by Androzej Ziabuke, Wiley and Sons, NewYork, N.Y. (1976); and "Encyclopedia of Polymer Science and Technology",Vol. 3, pps. 326-381.

The physical characteristics of the fiber may vary widely depending onintended use. For example, the fiber may have any cross-sectionalshapes, and may be circular, oval, rectangular, Y-shaped, dog-bone,hexalobal, trilobal, oblong, semi-torroidal, semispherical, semi-archedor the like. Fibers having a circular or oval cross-section may beuseful in wound closing applications; and fibers having a multilobalcross-section may be useful as filter components for blood in anextracorporeal loop or otherwise. Similarly, other cross-sectionaldimensions of the fiber such as numbers of lobes, porosity, whether thefiber is solid or hollow and surface properties such as roughness,smoothness, striations on the long axis, as well as circumferentialridges and valleys may also vary depending on the intended use. Forexample, smooth fibers having a solid cross-section may be important forfabrication of devices such as vascular graft; striated fibers may beused in the fabrication of devices as ligament or tendon prosthesis toencourage certain alignment of cells; and hollow fibers and multilobalfibers may be useful in the fabrication of device where absorbancy isneeded.

Fiber size is not critical and may also vary widely depending on theintended use. For example, fiber size may vary from sub-denier toribbons and tapes. The effective diameter of the fiber will usually varyfrom about 0.003 mm to about 6.0 mm. An effective diameter from about0.003 mm to about 4.0 mm is preferred.

The fibers of this invention may also have a multicomponent constructionin which at least one component is composed of one or more of thebiopolymers. These fibers include, but are not limited to, sheath-coreand multiple component fibers, multilayered types of fiber, hollowfibers and tubes having multicomponent layered construction and thelike. These multicomponent fibers are usually formed by co-extrusion oftwo or more biopolymers or one biopolymers and other materials. Suchco-extrusion techniques are known in the art and will not be describedin any detail.

The fibers of this invention may also be porous. These fibers can beformed by the addition of fillers, binders, additives and componentswhich were added to the biopolymer before or during fiber formationwhich are removed or leached from such fibers at some stage to form aporous or semi-porous system. In addition, gas foaming during theextrusion of the fibers either by gaseous foaming agents e.g., N₂, He,Ar, Ne, Air, and the like, or chemical foaming agents can be utilized toachieve a porous or somewhat porous structure.

The fibers of this invention may be used in monofialment form as forexample as a suture or a nerve channel which is extruded as a hollowfiber. Alternatively, the monofilament fiber of this invention may betowed, braided or twisted from one or more types of fibers, which arethen woven, braided and/or knitted into a variety of fibrous medicaldevices of this invention such as braided, knitted, woven or felted,fabrics or fibrillar products. These fibrous devices can be used as isor coated with other polymers or biopolymers prior to use.

Other characteristics of the fiber, such as denier, modulus, softness,tensile strength and the like depend on the end use of the fiber. Forexample, softened fibers are preferred in certain applications such aswound dressing, swabs, wound or burn covers, vascular grafts, and thelike. Fiber of different or the same polymeric compositions and physicaland mechanical properties but differing in denier can be obtained andused or fabricated into fabric that is woven, knitted, velvet, velour,mesh or braided. Staple fibers can be obtained and processed to fabricsuch as felt, mat and the like. For example, the felted material may beused as, or be part of, skin or wound covers, reinforcements forsuturing in surgery, and as aids for hemostasis. Velveted material isparticularly suited for use in small caliber blood vessel replacements.Matted fabric may be used, for example, as swabs.

The fibers of this invention are preferably used in the fabrication ofimplantable bioresorbable medical devices such as vascular implants,nerve channels; burn and wound covers; facial substitutes; orthopedicsubstitutes for bone or bone repair; breast prostheses; tendon andligament replacements; hernia patches; and the like, or used as suturesand fasteners. Other devices not necessary for implantation purposes canalso be formed from the fibers of this invention. The devices includecell culture substrates, absorbants or swabs, medicated dressings,gauze, fabric, sheet, felt or sponge for hemostasis, dental packs andthe like. Particularly useful devices are woven or knitted fabricsformed into tubes of varying shapes, lengths and diameters. Illustrativeof these devices are tubular prostheses such as vascular grafts, nerveguidance channels and the like. The particular configuration of suchtubes may vary according to the size and shape of the organ to berepaired, and whether the intended repair is to take place in humansurgery or in surgery involving other animal species.

Particularly preferred devices of this invention are solid extruded andfibrous vascular repair grafts. Such grafts can be fabricated inconventional configurations as for example as hollow tubes and tubulardevices formed from fabrics and the like, using conventional techniquesas for example extrusion, weaving, knitting and the like. For vasculargraft applications, the internal diameter commonly found useful is inthe range of from about 1.0 mm to about 30 mm.

In the preferred embodiments of the invention, especially for vasculargraft applications, the device is pre-treated to provide a morecomplaint prostheses. Any conventional method can be used. One preferredpretreatment method is crimping. Illustrative of useful crimping methodsis the method described in U.S. Pat. No. 3,337,673. In this method, thespacing and height can be controlled. The crimping ofcommercially-available Dacron vascular grafts (including both woven andknitted) was about one millimeter up and one millimeter down from themean diameter of the grafts. Crimping as such can be achieved by thismethod for the bioresorbable grafts. The vascular graft is preferablycoated with a bioresorbable biopolymer of this invention (especially theinternal surface) to improve graft patency. The coating is usually anamorphous bioresorbable biopolymer or biopolymer blend which has somesolubility in a solvent which is a non-solvent for the polymer orbiopolymers forming the graft body. The coating may be applied to thegraft by dissolving the coating biopolymer or biopolymer blend in asolvent which is a non-solvent for the graft polymer or biopolymer andthen dipping the graft body into the solution.

Other preferred devices of this invention are those which are useful inligament and tendon replacements. These devices are usually constructedof a fiber-like body composed of a relatively biodurable material suchas graphite, polyethylene or a relatively longer lasting butbioresorbable biopolymer fiber of this invention and the like coatedwith one or more bioresorbable or biodegradable biopolymers. Organizedtissue formation is encouraged by the use of the composites of thisinvention, which aids in regenerating ligaments and tendons.

Yet other preferred devices of the invention are those which are usefulin dental and orthopedic repair. In this application, the dental andorthopedic repair devices may be used in composite structures with orwithout such materials as calcium hydroxyapatite, Bioglass, calciumtriphosphate, drugs, and the like.

Still other preferred embodiments are devices for use as drug deliverysystem. Such drugs include drugs for control of body functions such asbirth control and other medicinal drugs. In these embodiments, the drugcan be dispersed in a bioresorbable biopolymer matrix having abioresorption rate such that the desired quantity of drug is releasedinto body as a function of time.

Other preferred devices of this invention are hollow fibers which areparticularly suited for use as nerve channels for the repair of severednerves. The diameters of the nerve channels will vary according to thesize and shape of the nerve to be repaired. U.S. Pat. No. 3,883,002discloses various sizes and shapes that may be employed. Lengths of thehollow fibers or tubes and their internal diameters and wall thicknesseswill also vary according to intended use. The length of the hollow fiberor tube is usually sufficient to bridge the size of the gap to berepaird and to allow extra tubing in which to insert nerve stumps.Particularly useful internal diameters commonly range from about 0.13 mmto about 5.00 mm. Particularly useful wall thicknesses are usually fromabout 0.01 mm to about 3.0 mm, and preferably from about 0.05 mm toabout 1.5 mm.

The preferred hollow fiber nerve channels may be formed from thebiopolymers by any conventional technique such as solution dipping on amandrel, melt extrusion, solution extrusion, gel extrusion, and thelike. However, it is particularly useful to employ an extrusion processwherein the hollow fiber or tube dimensions may be carefully controlledby the extruding die dimensions, differential gas pressure between innerand outer surfaces of the tube, melt draw down and subsequentorientation process. Die dimensions are easily selected by considerationof the inner and outer diameters of the nerve channel, die swell,extrusion rates and orientation in the melt and rubbery state. For nervechannels having desired dimensions and evenness, the usual procedure isto pressurize the tube with an inert gas to prevent collapsing. Thedifferential gas pressure is preferably maintained at about 0 to about0.02 atm, most preferably 0 to about 0.004 atm. The melt draw down maybe controlled by the ratio of average exit velocity out of the die andthe take up velocity. The exit velocity for a given die and polymer meltviscosity is controlled by the extrusion pressure. Orientation ispreferably effected by the ratio of speeds of two sets of rollers. Oftena draw pin or heated surface is present between the rollers to stabilizethe orientation process.

The devices of this invention are fabricated totally or in part frombiopolymers having at least one type of recurring monomeric unit havethe General Structures I or II: ##STR2## wherein Z, R₁, R₂, R₃, R₄, nand m are as described above.

Illustrative of useful R₁, R₂, R₃, and R₄ groups are hydrogen; alkylsuch as methyl, ethyl, propyl, butyl, pentyl, octyl, nonyl, tert-butyl,neopentyl, isopropyl, sec-butyl, dodecyl and the like; cycloalkyl suchas cyclohexyl, cyclopentyl, cyclooctyl, cycloheptyl and the like;alkoxyalkyl such as methoxymethylene, ethoxymethylene, butoxymethylene,propoxyethylene, pentoxybutylene and the like; aryloxyalkyl andaryloxyaryl such as phenoxyphenylene, phenoxymethylene and the like; andvarious substituted alkyl and aryl groups such as 4-dimethylaminobutyl,and the like;

Illustrative of other R₁ to R₄ groups are divalent aliphatic chains,which may optionally include one or more non-adjacent carbonyl, oxa,alkylaza, or arylaza groups such as --(CH₂)₂ --, --CH₂ C(O)CH₂ --,--(CH₂)₃ --, --CH₂ --CH(CH₃)--, --(CH₂)₄ --, --(CH₂)₅ --, --CH₂ OCH₂ --,--(CH₂)₂ --N(CH₃)CH₂ --, --CH₂ C(O)CH₂ --, --(CH₂)₂ --N(CH₃)--(CH₂)₂ --,1,4-cyclohexanediyl, 1,5-cyclooctanediyl, 1,3-cyclopentanediyl,1,3-cyclohexanediyl, 2,2-dimethyl-1,5-cyclopentanediyl and the like, toform fused, spiro, bicylic and/or tricyclic ring systems and the like.

Illustrative of useful R₅ and R₆ groups are the above-listedrepresentative R₁ to R₄ groups, including --OCH₂ C(O)CH₂ --, --(CH₂)₂--NH--, --OCH₂ C(O)CH₂ --, and --O--(CH₂)₂ --O-- and the like; alkoxysuch as propoxy, butoxy, methoxy, isopropoxy, pentoxy, nonyloxy, ethoxy,octyloxy and the like; dialkylamino such as dimethylamino,methylethylamino, diethylamino, dibutylamino and the like; alkylcarbonylsuch as acetyl, and the like; arylcarbonyl such as phenylcarbonyl,p-methylphenyl carbonyl and the like; and diarylamino and arylalkylaminosuch as diphenylamino, methylphenylamino, ethylphenylamino and the like.

Preferred for use in the practice of this invention are devices formedtotally or in part from homopolymers or copolymers formed from at leastone type of recurring unit of the Structure I or Structure II wherein:

Z is --C(R₅ R₆)--, --O-- or a combination thereof,

where Z is selected such that there are no adjacent heteroatoms;

m is 1, 2, 3 or 4;

n is 1, 2 or 3; and

R₁ to R₆ are as defined above, preferably where aliphatic moietiesincluded in R₁ to R₆ include up to about 10 carbon atoms and arylmoieties include up to about 16 carbon atoms.

Illustrative of biopolymers for use in the fabrication of the preferreddevices of this invention are those formed from at least one type ofrecurring monomeric unit of the Structure I wherein n is 1 and Z is ofthe formulas: ##STR3## wherein:

--C-- denotes the center carbon atom of Z, when Z is --[C(R₅ R₆)]--;

R₇ is the same or different and is aryl, alkyl or an alkylene chaincompleting a 3 to 16 membered ring structure, including fused, spiro,bicyclic and/or tricyclic structures, and the like;

R₈ and R₉ are the same or different at each occurrence and are R₇ orhydrogen; and

s is the same or different at each occurrence and is 0 to about 3, andthe open valencies are substituted with hydrogen atoms.

Also illustrative of the preferred devices of this invention are thoseformed totally or in part from biopolymers comprising at least one typeof recurring unit of the formula: ##STR4## wherein:

R₁, R₂, R₃, and R₄ are the same or different at each occurrence and arehydrogen, alkyl such as methyl, ethyl, n-propyl, nonyl, isopropyl,n-butyl, sec-butyl, tert-butyl, neopentyl, and the like; phenyl;phenylalkyl, such as benzyl, phenethyl, and the like; phenyl substitutedwith one or more alkyl or alkoxy groups such as tolyl, xylyl,p-methoxyphenyl, m-ethoxyphenyl, p-propoxyphenyl,1-methoxy-4-methylphenyl, and the like; and alkoxyalkyl such asmethoxymethyl, ethoxymethyl and the like;

R₅ and R₆ are the same or different and are R₁ to R₄, alkoxy, alkanoyl,arylcarbonyl or dialkylamino; or R₁ to R₆ together may form alkylenechain completing 4, 5, 6, 7, 8 or 9 membered spiro, bicyclic and/ortricyclic ring structure, which structure may optionally include one ormore non-adjacent divalent carbonyl, oxa, alkylaza or arylaza groups;with the proviso that when said biopolymer is a copolymer havingrecurring monomeric units of the Structure I derived from trimethylenecarbonate the other recurring units of said copolymer are not derivedfrom glycolic acid or glycolide.

n is 1, 2 or 3; and

m is 1 to about 6:

Particularly preferred for use in the practice of this invention aredevices fabricated totally or in part from biopolymers comprising atleast one type of recurring unit of the formula: ##STR5## wherein:

R₁ to R₄ are the same or different and are alkyl, hydrogen, alkoxyalkyl,phenylalkyl, alkoxyphenyl or alkylphenyl, wherein the aliphatic moietiesinclude from 1 to about 9 carbon atoms;

R₅ and R₆ are the same or different at each occurrence and are selectedfrom the group consisting of R₁ to R₄ substituents, aryloxy, and alkoxy,or R₅ and R₆ together may form an aliphatic chain having from about 3 toabout 10 membered spiro, bicyclic and/or tricyclic structure which mayinclude one or two non-adjacent carbonyl, oxa, alkylaza or arylazagroups; with the proviso that when said biopolymer is a copolymer havingrecurring monomeric units of the Structure I derived from trimethylenecarbonate the other recurring units of said copolymer are not derivedfrom glycolic acid or glycolide.

n is 1 to about 3; and

m is 1 to about 6.

In the most preferred embodiments of this invention, the device isformed totally or in part from biopolymers comprising at least one typeof recurring monomeric unit of the Structures II or III: ##STR6##wherein:

n is 1 to about 3;

m is 1 to about 4;

R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are hydrogen,aryl, alkylaryl, arylalkyl, or alkyl, or R₅ and R₆ together make adivalent chain forming about 3 to about 10 membered spiro, bicyclic,and/or tricyclic ring structure which may include one or twonon-adjacent carbonyl, oxa, alkylaza or arylaza groups, with the provisothat when said biopolymer is a copolymer having recurring monomericunits of the Structure I derived from trimethylene carbonate, the otherrecurring units of said copolymer are not derived from glycolic acid orglycolide.

It is more preferred that the device is formed totally or in part of oneor more biopolymers having at least one type or recurring monomeric unitof Structure II or III, where R₁ to R₆ are the same or different at eachoccurrence and are hydrogen, alkyl, alkylaryl, arylalkyl or aryl; or R₅and R₆ together may form a divalent chain forming an about 3 to about 10membered, preferably from about 5 to about 7 membered alicyclic, spiroand/or bicyclic ring structure which may optionally include one or twonon-adjacent oxa, carbonyl, alkylaza or arylaza functional groups. It isparticularly preferred that the device be formed totally or in part ofone or more of biopolymers having recurring unit of the Structure II orIII in which R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and arehydrogen, aryl or alkyl, alkylaryl having from 7 to about 14 carbonatoms such as tolyl or phenyl; or lower alkyl of from 1 to about 7carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl,tert-butyl, pentyl, neopentyl, hexyl and sec-butyl.

In the most preferred embodiments of this invention, biopolymers used inthe fabrication of the device has recurring unit of the Structures II orIII, where n is 1, 2 or 3; m is 1 or 2 and R₁ to R₆ are the same ordifferent and are hydrogen or lower alkyl having from about 1 to about 7carbon atoms which do not differ from each other by more than about 3carbon atoms, and preferably which do not differ by more than about 2carbon atoms. In these embodiments, it is particularly preferred that R₁to R₄ and R₅ to R₆ are the same and are hydrogen or alkyl of from about1 to about 4 carbon atoms, n is 1, 2 or 3; and m is 1 or 2; and it ismost preferred that R₁ to R₆ are methyl, ethyl or hydrogen; n is 1, 2 or3; and m is 1 or 2.

The devices of this invention may be fabricated from one biopolymer orblends or composites may be used. Such blends and composites allowmanipulations of various properties as for example bioresorption rate ofthe device, toughness of the device, pliability or elasticity of thedevice and the like.

The device of this invention may be fabricated from homopolymers havingrecurring units of Structures I and II. Alternatively, the device may befabricated from block or random copolymers which including one or moretypes of recurring units of Structures I and/or II and at least oneother type of recurring unit which may be bioresorbable ornon-bioresorbable; or the device may be fabricated from random or blockcopolymers which include more than one type of recurring monomeric unitof Structure I or Structure II. Such copolymers can be random copolymersor may be block copolymers depending on the properties of the polymerrequired for the particular application. Illustrative of usefulcopolymers are random copolymers comprising one or more monomeric unitsof the Structures I or II and comprising one or more other types ofbioresorbable monomeric units, as for example units derived fromα-hydroxy carboxylic acids, dioxepanones, dioxanones, and the like, orone or more other types of recurring monomeric units of the Structure Iand/or II. Also illustrative of copolymers useful in the fabrication ofthe device of this invention are block copolymers comprising one or more"A" blocks which may be formed of recurring units of Structures I andII, and one or more "B" blocks which may be formed from other types ofbioresorbable recurring monomeric units, or which may be formed from oneor more other types of recurring units of Structure I and II. Each "A"block and each "B" block may be the same or different. As used herein,the term "block" means a sequence of one type of monomeric unit at leastabout 5 monomeric units long, or such sequence of two or more types ofrecurring monomeric units either randomly distributed in such a sequenceor distributed such sequence in a block-like fashion. Each "A" block and"B" block may comprise a single type of recurring monomeric unit.Alternatively, each block may comprise more than one type of recurringmonomeric unit, randomly distributed throughout each block. For example,the block copolymers as described above may have repeating block unitssuch as AB, ABA, BAB, ABAB, ABABA, BABAB, and the like, where each "A"block and each "B" block contains the same or substantially the sametypes of recurring monomeric unit, and/or where each block contains thesame or substantially the same number of recurring units. Alternatively,the various "A" and "B" blocks contained in the block copolymers mayhave more than one type of "A" block or "B" block, each of which maycontain a different type or types of recurring monomeric units; or eachblock may contain the same or different types of recurring units buthave differing number of recurring units in each block. With respect tothe recurring blocks of A's and B's, each of them may also be the sameor different. For example, ABABA may in fact be MNOPQ, ABA may be MNQ orABA may be MNOPQ, where M, N, O, P and Q are the same or differentprovided that at least one of M, N, O, P and Q is a recurring unit ofthe Structure I or II. Especially preferred are block copolymers ofstructures AB and ABA, with ABA being the most preferred.

In the preferred embodiment of this invention, the biopolymers of choiceare copolymers; and block copolymers are especially preferred. Throughuse of selected monomeric units and their arrangement in the polymerchain, thermal history, mechanical processing and treatment of thebiopolymers and the devices fabricated from the biopolymers, theproperties of the biopolymer such as elasticity, modulus, pliability,hardness, softness and crystallinity, and the bioresorption rate of thebiopolymers can be tailored and optimized for any particularapplication.

The other type of recurring monomeric units contained in the copolymersmay vary widely and may be bioresorbable or nonbioresorbable. In thepreferred embodiments of the invention the other types of recurringmonomeric units are bioresorbable. Illustrative of the other type ortypes of recurring monomeric units are those which are derived frommonomers which polymerize by ring opening polymerization as, forexample, substituted and unsubstituted beta, gamma, delta, omega, andother lactones such as those of the formula: ##STR7## where R₁₀ isalkoxy, alkyl or aryl, and q is 0 to about 5, wherein the open valenciesare substituted with hydrogen atoms. Such lactones includecaprolactones, (d or l) 3-methylpropiolactone, (d or l)3-ethyl-1-propiolactone, pivalolactone, valerolactones, butyrolactones,propiolactones and the lactones of hydroxy carboxylic acids such as3-hydroxy-2-phenylpropanoic acid, 3-hydroxy-3-phenylpropanoic acid,4-hydroxybutanoic acid, 3-hydroxybutanoic acid,3-hydroxy-3-methylbutanoic acid, 4-hydroxypentanoic acid,5-hydroxypentanoic acid, 3-hydroxy-4-methylheptanoic acid,4-hydroxyoctanoic acid, and the like; and lactides such as l-lactide,d-lactide, and d,l-lactide; glycolide; and dilactones such as those ofthe formula: ##STR8## where R₁₀ and q are as defined above and where theopen valencies are substituted with hydrogen atoms. Such dilactonesinclude the dilactones of 2-hydroxycarboxylic acids such as2-hydroxybutyric acid, 2-hydroxy-2-phenylpropanoic acid,2-hydroxyl-3-methylbutanoic acid, 2-hydroxypentanoic acid,2-hydroxy-4-methylpentanoic acid, 2-hydroxyhexanoic acid,2-hydroxyoctanoic acid, and the like.

Illustrative of still other useful recurring units are those derivedfrom dioxepanones such as those described in U.S. Pat. No. 4,052,988 andU.K. Patent No. 1,273,733. Such dioxepanones include alkyl and arylsubstituted and unsubstituted dioxepanones of the formula: ##STR9## andmonomeric units derived from dioxanones such as those described in U.S.Pat. Nos. 3,952,016, 4,052,988, 4,070,375, and 3,959,185, as forexample, alkyl or aryl substituted and unsubstituted dioxanones of theformula: wherein q is as defined above; R₁₀ is the same or different ateach occurrence and are hydrocarbyl groups such as alkyl and substitutedalkyl, and aryl or substituted aryl; and the open valencies aresubstituted with hydrogen atoms. Preferably R₁₀ is the same or differentand are alkyl groups containing from 1 to 6 carbon atoms, preferably 1or 2 carbon atoms, and q is 0 or 1.

Suitable for use in such copolymers are monomeric units derived fromethers such as 2,4-dimethyl-1,3-dioxane, 1,3-dioxane, 1,4-dioxane,2-methyl-5-methoxy-1,3-dioxane, 4-methyl-1,3-dioxane,4-methyl-4-phenyl-1,3-dioxane, oxetane, tetrahydrofuran,tetrahydropyran, hexamethylene oxide, heptamethylene oxide,octamethylene oxide, nonamethylene oxide, and the like.

Also useful are monomeric units derived from epoxides such as ethyleneoxide, propylene oxide, alkyl substituted ethylene oxides such as ethyl,propyl, and butyl substituted ethylene oxide, the oxides of variousinternal olefins such as the oxides of 2-butene, 2-pentene, 2-hexene,3-hexene, and like epoxides. Still other useful monomeric units arethose derived from epoxides/carbon dioxide such as ethylene oxide/CO₂and its ethylene carbonate equivalent, and propylene oxide/CO₂ and itspropylene carbonate equivalent; and monomeric units derived fromorthoesters and orthocarbonates such as unsubstituted alkyl or arylsubstituted orthoesters, orthocarbonates and cyclic anhydrides (whichoptionally include one or more oxa, alkylaza, arylaza, and carbonylgroups) of the formula: ##STR10##

where q and R₁₀ are as described above, r is 0 to about 10, R₁₃ is thesame or different at each occurrence and is alkyl or aryl, and R₁₁ andR₁₂ are the same or different and are hydrogen, alkyl or aryl.

Monomeric units derived from precursors and derivatives of lactides,lactones, dioxanones, orthoesters, orthocarbonates, anhydrides, anddioxepanones such as the various hydroxycarboxylic acids, substituted ornon-substituted diacids such as oxa, aza, alkyl, aryl, substituteddiacids, hydroxy substituted oxacarboxylic acids, functionalized esters,and acid halide derivatives, and the like can also be used othermonomeric component of the copolymer.

Preferred copolymers used in fabricating the device of this inventionare those which include two or more types of recurring monomeric unitswithin the scope of Structures I and II, but those which include one ormore types of recurring units of Structures I and II and one or moreother types of bioresorbable recurring monomeric units derived fromlactones, lactides and their precursors; orthoesters; dioxepanones;carbonates other than those of the Structures I and II; dioxanones; andorthocarbonates. Particularly preferred for use in the practice of thisinvention are copolymers comprising one or more types of recurring unitsof the Structures II or III, and one or more types of recurringmonomeric units derived from gamma, delta and omega lactones and theirprecursor acids such as caprolactone, valerolactone, butyrolactone,3-hydroxybutanoic acid, 4-hydroxybutanoic acid, propiolactone, (d or l)3-methylpropiolactone and the like; lactides and their precursor acidssuch as 1-lactide, d-lactide, d,l-lactide, 2-hydroxyisobutyric acid,2-hydroxy-2-phenylpropanoic acid, and the like; dioxepanones;dioxanones; carbonates other than those of the Structure I and II;orthoesters; and orthocarbonates. Other particularly preferredcopolymers for use in the practice of this invention are thosecomprising two or more recurring units of the Structures II and III suchas dimethyltrimethylene carbonate/trimethylene carbonate copolymer.

Most preferred for use in the practice of this invention are random orblock copolymers comprising one or more types of recurring monomericunits of the Structure III where R₅ and R₆ are the same or different andare hydrogen, methyl or ethyl and one or more other types of recurringmonomeric units derived from lactones (preferably valerolactone,caprolactone, unsubstituted and alkyl substituted propiolactone andpivalolactone; lactides or their precursors; and carbonates other thanthose of the Structures I and II. Other most preferred devices of thisinvention are those formed totally or in part from block or randomcopolymers comprising two or more types of recurring monomeric units ofthe Structure III, in particular those having at least one type ofrecurring monomeric unit of the Structure III in which n is 1 and R₅ andR₆ are alkyl (such as units derived from dimethyltrimethylenecarbonate), and at least one type of recurring monomeric unit of theStructure III in which n is 1 to about 3, and R₅ and R₆ are hydrogen,such as trimethylene carbonate, tetramethylene carbonate andpentamethylene carbonate.

The types of recurring monomeric units and molecular weight of thebiopolymer, as well as the relative percentages of each of the recurringmonomeric units in the copolymers used in the fabrication of the deviceof the invention may vary widely depending on the particular device andthe desired characteristics of the copolymer or homopolymer. The typesand quantities of recurring units and the molecular weight impact on thephysical properties of the biopolymer such as tensile strength, modulus,hardness, elasticity, softness, toughness, compliancy, crystallinity,bioresorption rate and the like as needed for optimized or at leastacceptable performance of the device. These properties, in turn, will bedeterminative of the characteristics of the device and the suitabilityand efficacy for use in any application. Various types and amounts ofrecurring monomeric units can be conveniently selected to tailor theproperties of the copolymer to optimize the desirable propertiesrequired for any device.

While we do not wish to be bound by any theory, it is believed thatwhether it is random or block copolymer or a homopolymer, the higher thecontent of monomeric units of the Structure I or II wherein R₁ to R₄ arehydrogen, Z is --C(R₅ R₆)-- wherein R₅ and R₆ are hydrogen; n is from 1to 5; and m is from 1 to 5 the more flexible and soft the biopolymerwill be. Conversely, in such random or block copolymers or homopolymers,the higher the content of monomeric units if the Structure II where m is1 and R₁ to R₄ are hydrogen; and of the Structure I where R₁ to R₄ arehydrogen or alkyl, and Z is [--C(R₅ R₆ ] wherein R₅ and R₆ are the sameand are alkyl or phenyl or R₅ and R₆ together form an alkylene chainwhich may optionally include one or more oxa groups completing a spiroring structure the harder and more crystalline the biopolymer. Forexample, in those instances where a soft, pliable and relatively fastbioresorbing copolymer is required as for example as a coating on aDacron vascular graft, monomeric units such as those of the StructureIII where n is 1 to 3 and R₅ and R₆ are hydrogen are selected and areincorporated into the copolymer in a major amount. Similarly, soft andpliable coatings and devices can be obtained from a homopolymer oftrimethylene carbonate, random copolymers of trimethylene carbonate andlactide (90:10), block copolymers of trimethylene carbonate and lactide(95:5), and random and block copolymers of dimethyl trimethylenecarbonate and trimethylene carbonate (56:44).

In other situation where toughness and a slower bioresorption rate isdesired as for example in a stent, a tendon or ligament replacementdevice, orthopedic plates and pins, monomeric units such as those of theStructure III where n is 1 and R₅ and R₆ are alkyl such as methyl areselected and incorporated into the copolymer in a major amount, andmonomeric units, such as those of the Structure III where n is 1 and R₅and R₆ are hydrogen in the minor amount. For example hard andcrystalline devices can be obtained from a homopolymer ofdimethyltrimethylene carbonate, or random copolymers ofdimethyltrimethylene carbonate and trimethylene carbonate,dimethyltrimethylene carbonate/caprolactone, dimethyltrimethylenecarbonate/tetramethylene carbonate and ABA block copolymers ofdimethyltrimethylene carbonate/trimethylenecarbonate/dimethyltrimethylene carbonate, dimethyltrimethylenecarbonate/lactides/dimethyltrimethylene carbonate, dimethyltrimethylenecarbonate/lactides, trimethylene carbonate/dimethyltrimethylenecarbonate, and l-lactide/trimethylene carbonate/l-lactide.

In general, in the preferred embodiments of this invention, recurringunits of the Structure I, Structure II or Structure III are in the"major amount". As used herein, "major amount" is more than about 50 wt.% based on the total weight of all recurring monomeric units in thecopolymer. In the preferred embodiments of the invention, the amount ofrecurring units of Structure I, Structure II and Structure III may rangefrom greater than about 50 wt. % to about 100 wt. %, based on the totalweight of recurring units in the copolymer, more preferably from about80 wt. % to about 100 wt. %, and most preferably from about 85 wt. % toabout 99 wt. %.

Useful average molecular weight ranges of biopolymers for use in anyparticular situation will vary depending on the desired characteristicsof the biopolymer. In general, physical properties such as modulus,tensile strength, crystallinity and the like require a certain minimummolecular weight, which will vary with each biopolymer. Above thisminimum, the properties do not depend strongly on molecular weight. Meltviscosity and solution viscosity increase with increasing molecularweight useful for a particular polymer. For this reason, there usuallywill be a maximum molecular practical weight because of the difficultyof processing it into the desired articles by conventional technology.Within the range of useful molecular weights, the rate of bioresorptionwill vary with the molecular weight and the crystallinity. Highermolecular weight and more crystalline or less crystalline biopolymerswill require longer times to bioresorb than lower molecular weightbiopolymers. The desired period of time over which the device willdictate the choice of molecular weight.

In general, the devices of this invention are formed totally or in partof biopolymers of the Structure I or II that can range in molecularweight from low molecular weight to extremely high molecular weight.Molecular weights of biopolymers for use in the practice of thisinvention usually are equal to or greater than about 5,000. Preferredaverage molecular weight ranges are from about 7,000 to about 5,000,000,with a range of from about 10,000 to about 500,000 being particularlypreferred, and a range of from about 15,000 to about 250,000 being mostpreferred.

Other components may be combined with the biopolymers before they areformed into the devices of the invention, or added to, coated onto andthe like, during or after their formation. These components includesubstances that will not interfere with the desired properties of thebiopolymers, e.g., their ability to degrade into components biologicallyinnocuous to living systems. Among the contemplated classes of suchsubstances are placticizers, stabilizers for UV or temperature,pigments, lubricants and antioxidants. One of skill in the art willappreciate that any additives included in the medical devices of theinvention, should be those that would meet with FDA approval.

Other optional polymeric components such as fibers, fillers and bindersmay be combined with the biopolymers prior to and during the formationthe devices, or subsequent to their formation. These include, but arenot limited to polymers and copolymers selected from the groupconsisting of polyesters such as poly(butylene terephthalate) andpoly(ethylene terephthalate); poly(vinyl alcohol); poly(vinyl acetate)and partially hydrolyzed forms thereof; hydrogel type polymers such aspoly(hydroxyethyl methacrylate), poly(hydroxypropyl methacrylate), andthe like; polysulfones such as poly(phenylenesulfone); carbon; siliconcarbide; halopolymers such as poly(tetrafluoroethylene),ethylene/tetrafluoroethylene copolymer; poly(dioxanone);poly(glycolide-co-trimethylene carbonates); poly(lactides);poly(d-lactide); poly(l-lactide); poly(lactide-co-caprolactone);poly(d,l-lactide); poly(caprolactones); poly(hydroxybutyrates);poly(hydroxyvalerates); poly(hydroxybutyrate-co-hydroxyvalerates);poly(glycolide); poly(urethanes); segmented poly(urethanes);poly(etherurethanes); poly(urethane ureas); silicone rubber; andsubstances such as fibrin and its powder; natural or processed collagen;mono-, di-, tri-, and poly (saccharides); poly(ethylenes); poly(amides);poly(propylene); peptides such as nerve growth factors, bone growthfactors, laminin, and the like; poly(carbonates); poly(vinyl fluoride);poly(vinylidene fluoride); poly(vinyl butyral); cellulose such as,carboxylmethyl cellulose, cellulose acetate, ethylcellulose, and thelike; ethylene vinylacetate copolymers and hydrolyzed and partiallyhydrolyzed forms thereof; poly(acrylonitrile); poly(vinyl methyl ether);and their derivative copolymers, blends, composites, and the like.

Other biocompatible components besides polymeric components may becombined with the polymers during or before they are formed into thedevices of the invention, or added to, coated onto and the like, aftertheir formation. These components include substances that will enhancecertain of the desired properties of devices made from the biopolymers.Illustrative of such substances are plasticizers, lubricants,antioxidants, stabilizers of all kinds such as stabilizers for UVradiation, heat, moisture, and the like, as well as drugs for treatmentof certain disorders or diseases and growth factors such as those fornerve and bone, and growth hormones in general. Materials such ascalcium phosphate salts, ceramics, bioresorbable or otherwise, such ascalcium hydroxyapatite, Bioglass, and calcium triphosphate may also becombined with the biopolymer. Components such as certain barium salts torender devices formed with them radio-opaque are also within thecontemplation of the invention. Certain of these fillers, binders,additives and components can be removed or leached from suchbiopolymeric devices at some stage, so that a porous or semi-poroussystem can be obtained.

Devices of this invention may be fabricated totally from the biopolymersof the Structure I or II or may be fabricated in part from otherbioresorbable materials or from biodurable materials which arerelatively resistant to biodegradation. Illustrative of biodurablematerials useful in the fabrication of devices of this invention aresilicone, silicone rubber, poly(ethylene), poly(ethylene terephthalate),poly(fluoroethylenes), poly(phosphazene), poly(urethane), segmentedpoly(urethane), and the like. Also useful are biodurable metallicsubstances such as titanium, stainless steel, and alloys such aschrominium-cobalt-molybelenum alloys, titanium-aluminum-vanadium alloys,and the like.

The following are more specific examples of various embodiments of theinvention and are not to be considered limitative thereof.

EXAMPLE 1 Synthesis of 5,5-Dimethyl-1,3-dioxan-2-one(Dimethyltrimethylene Carbonate (DMTMC)).

A three liter three-necked round bottom flask was fitted with mechanicalstirrer, 12 inch Vigreux column with distilling head and a thermometer.In the flask were placed 838 g (8.05 miles) 2,2-dimethyl-1,3-propanedioland 1098 mL (9.07 moles) diethyl carbonate. The mixture was immersed inan oil bath, heating initiated, and the stirrer started. By the time thetemperature reached about 90° C., the diol had melted and dissolved inthe carbonate. Powdered, dry sodium methoxide (21.6 g, 0.4 moles) wasadded through the neck used for the thermometer. The bath temperaturewas raised to 160° C.; ethanol began to distill out.

Over a period of about three hours, approximately 600 g (80% oftheoretical) of distillate was collected; this is mainly ethanol withsome diethyl carbonate. The reaction mixture gradually became verythick. Dry xylene (200 mL) was added through the top of the distillingcolumn and the bath temperature was raised to 170°-180° C. Additionaldistillate was collected and the pot temperature gradually climbed toabout 150° C.; when the distillation rate had slowed to only a few dropsa minute, vacuum was cautiously applied to the system and graduallyincreased as the xylene and excess diethyl carbonate distilled out.

When the vacuum reached about 2-5 mm Hg, the product carbonate began todistill at about 125°-135° C. At this point, the vacuum was releasedwith dry nitrogen and the oil bath lowered. The Vigreux column anddistilling head were removed and replaced with a short path distillationhead. Additional powdered sodium methoxide (5.4 g, 0.1 moles) was addedquickly through the thermometer port.

Vacuum was applied to the system and adjusted to about 3-5 mm Hg.Heating was resumed and the product began to distill out. The bathtemperature was raised to 210°-220° C. gradually in order to maintainthe depolymerization rate of the oligomers to generate the productmonomer. Care had to be taken not to rush the distillation, so thatdepolymerization of the dimer and oligomers could occur; otherwise, thedimer would have begun to distill over. Eventually, the pot residuebecame a gummy lump coated with powder and distillation ceased. Totalyield of distillate was 852 g (81% of theory).

The product was a slightly sticky solid due to contamination with smallamounts of impurities, such as xylene, diethyl carbonate, the startingdiol and the cyclic dimer. It was recrystallized as follows. The totalcrude DMTMC (852 g) was dissolved in 430 mL tetrahydrofuran and 4.3liters of anhydrous diethyl ether was added cautiously. The liquors wereallowed to stand at room temperature for about one-half hour, thenplaced in a refrigerator at 4° C. overnight. The crystals were collectedby filtration, washed with cold ether (1.2 liters), with hexane (1.2liters), and then by pulling air through the filter cake for about onehour. Final drying was in a vacuum oven at 35°-40° C. (0.1 mm Hg). Totalrecovery of purified DMTMC was 730 g (70% overall yield).

EXAMPLE 2 Synthesis of 1,3-Dioxan-2-one (Trimethylene Carbonate (TMC))

A 1-liter three-neck round bottom flask was fitted with mechanicalstirrer and a 12 in. Vigreux column topped with a distilling head havinga stopcock for controlling the reflux ratio. The flask was charged with1,3-propanediol (228.3 g, 3 mol) and diethyl carbonate (454 mL, 3.75mol), flushed with nitrogen, then immersed in an oil bath. Heating wasinitiated and, when the temperature had reached about 80° C., sodiummethoxide (1.62 g, 30 mmol) was added via funnel through the third neck.The oil temperature was raised to 155°-160° C., and ethanol soon beganto reflux.

Ethanol was removed gradually over a period of about 3.5 hrs. underpartial reflux. Takeoff cannot be too fast, as the temperature risesfrom about 80° C. as the distillate becomes rich in diethyl carbonate. Atotal of 268 grams of distillate was collected, with about 80-85%ethanol and the remainder carbonate by NMR. Additional sodium methoxide(0.40 g, 7.4 mmol) was cautiously added at this point and heating wascontinued for another 30 mins. A slight vacuum was carefully applied,and additional distillate collected. The vacuum was gradually increaseduntil the pressure was down to about 1 mm, by which time most of theremaining diethyl carbonate was removed.

The oil bath was lowered and stirring continued for about 15 min.(temperature was not monitored). Triethylamine hydrochloride (5.2 g, 38mmol) was added and stirring continued for 45 min. without heating.Stannous octoate (15 drops, about 0.2 grams) was added, heating resumed(bath at 150° C. initially, increasing to 200° C.), and a vacuumgradually applied to about 0.5 mm. An initial forecut boiling 70°-125°C. (25 g) was rejected, while the main fraction (245 g) collected at125°-135° C. (0,5 mm) was about 85% pure by NMR. The residue from thedistillation was dissolved in chloroform, filtered and distilled in aKugelrohr at 160°-220° C. (0.1 mm) to give an additional 25 grams ofdioxanone.

The main fraction was recrystallized from 1:1 ether: THF (4 mL/g) togive 168 g of dioxanone of high purity. Evaporation of the filtrate andtrituration with ether-THF (about 4:1) gave an additional 45 g of crudeproduct, which was combined with the 25 grams obtained from cracking ofthe residue. Recrystallization from ether-THF gave 46.5 g of puredioxanone. The combined 214.5 grams of dioxanone was distilled in theKugelrohr at 120°-130° C. (0.1 mm) to give 209.3 g (68% of theory)polymer grade product.

EXAMPLE 3 Polymerization of DMTMC

A freshly purified and dried sample of dimethyltrimethylene carbonate(12.1 g, 90 mmol) was loaded into a 15 mL polymerization tube. The tubewas connected to a vacuum line via a rubber tubing and a stopcock,evacuated, and the DMTMC melted carefully with a heatgun. The tube wascooled in ice water, evacuated again, remelted, and cooled in ice.Vacuum was released with argon, the stopcock removed, and a solution ofstannous octoate in toluene (100 μL of 3.0×10⁻² M solution, 0.003 mmol)was added. The stopcock was reattached, the tube evacuated for severalminutes to remove the toluene, then sealed with a torch. The contents ofthe tube were melted and thoroughly mixed, then the tube was immersed inan oil bath at 160° C. for 18 hours, cooled and broken. The polymer wasdissolved in 250 mL chloroform, precipitated into 2 L of 2-propanol,washed with additional 2-propanol and dried in a vacuum oven at 50° C.The resulting powdery polymer (10 g, 83%) had a reduced viscosity of 3.0dL/g (0.1% solution in dioxane).

EXAMPLE 4 Poly(TMC)

A freshly distilled sample of trimethylene carbonate (10.9 g, 107 mmol)was melted in a round bottom flask under argon and transferred viasyringe into a 15 mL polymerization tube. The tube was connected to avacuum line via rubber tubing and a stopcock and evacuated. The tube wascooled in ice water, evacuated again, remelted, and cooled in ice.Vacuum was released with argon, the stopcock removed, and a solution ofstannous octoate in toluene (250 μL of 1.3×10⁻² M, 0.003 mmol) wasadded. The stopcock was reattached, the tube evacuated for severalminutes to remove the toluene, then sealed with a torch. The contents ofthe tube were melted and thoroughly mixed, then the tube was immersed inan oil bath at 160° C. for 18 hrs, cooled and broken. The polymer wasdissolved in 250 mL chloroform, precipitated into 2 L of 2-propanol,washed with additional 2-propanol and dried in a vacuum oven at 50° C.The resulting rubbery polymer (10 g, 83%) had a reduced viscosity of2.13 dL/g (0.1% solution in dioxane). GPC analysis versus polystyrenestandards gave an approximate weight average molecular weight of 91,000.

EXAMPLE 5 Fiber Spinning

The DMTMC homopolymer of Example 3 was melt spun at 160° C. into a 70denier filament. The material appears to crystallize very rapidly.Sections of yarn were hand drawn to approximately 30 denier and tested.Satisfactory fiber properties for fabric and hollow fiber applicationswere achieved. Fiber properties are: Denier (55); Tensile Modulus (59grams/denier); Tensile Strengh (3 grams/denier); Ultimate Elongation(26%).

EXAMPLE 6 Poly (TMC-co-l -Lactide)

Freshly distilled trimethylene carbonate (12.95 g, 127 mmol) was meltedtogether with dried, recrystallized l-lactide (2.03 g, 14.1 mmol), thenthe mixture was syringed into a 15 mL polymerization tube. The catalyst(73 μL of 3.0×10⁻² M stannous octoate in toluene) was added, then thetube was degassed by freezing, pumping and thawing twice. After sealingunder vacuum, the tube was immersed in an oil bath at 160° C. for 60hours. The tube was cracked and 10 g of the crude polymer was dissolvedin chloroform (250 mL), then precipitated into isopropanol. The driedpolymer, 8.6 g, had a reduced viscosity of 1.53 dL/g (0.1% solution indioxane).

In another experiment, freshly distilled trimethylene carbonate (12.95g), 2.03 grams of recrystallized L-lactide and 7.5 μl of 1.0M stannousoctoate in toluene was placed inside a 160° C. oil bath for 16 hrs. Theampule was cracked and 12.9 grams was the final yield after twicereprecipitated from tetrahydrofuran (THF) solution. The weight averagemolecular weight was 87,000 and number average molecular weight was13,760 by GPC in THF. The GPC system was calibrated with polystyrenestandards.

EXAMPLE 7 Copolymerization in sealed tube of DMTMC and TrimethyleneCarbonate (TMC), 97.5:2.5

A mixture of freshly purified and dried DMTMC (14.64 g, 112.5 mmol), TMC(378 mg, 3.7 mmol), and 2,2-dimethylpropanediol (12 mg, 0.116 mmol) wascombined in a polymerization tube, evacuated, and the tube filled withargon. Stannous octoate (65 μL of 3×10⁻² M solution in toluene) wasadded and the tube evacuated for several minutes. The tube was sealedwith a torch, the contents melted and thoroughly mixed, then immersed inan oil bath at 160° C. overnight. After chilling in liquid nitrogen, thetube was broken, the contents were dissolved in dioxane (250 mL), andprecipitated into 1 L of ice water. The polymer was washed with water(2×500 mL) and dried in vacuo overnight at 50° C. Yield: 13.1 g (87%);reduced viscosity 0.68 dL/g (0.1% in dioxane). [Sample 9, Table I]

EXAMPLE 8 Copolymerization in resin flask of DMTMC and TMC, 97.5:2.5

An oven-dried, silanized glass 150 mL resin flask was equipped withmechanical stirrer and a teflon paddle, argon inlet, a serum cap on oneport, and a glass stopper on the remaining port. To the flask were addedfreshly dried and purified DMTMC (29.25 g, 225 mmol), TMC (0.75 g, 7.4mmol), and dimethylpropanediol (12 mg, 0.12 mmol). The flask wasevacuated and filled with argon several times, then immersed in an oilbath at 120° C. to melt the monomers. The temperatures was raised to145° C. in 10 minutes, then 125 μL of a 3×10⁻² M solution of stannousoctoate in toluene was added. The temperature was raised to 160° C. inanother 10 minutes. Within another 10 minutes the material had becomevery thick and after one hour the reaction was stopped, the polymer wasdissolved in chloroform and precipitated into 2-propanol. Yield: 24.4 g,(81%); reduced viscosity 0.80 dL/g (0.1 % in dioxane). [Sample 10, TableI].

EXAMPLE 9 Poly(DMTMC co TMC), 97.5:2.5

A polymerization was carried out as in the preceding example, with thefollowing changes. The resin kettle was of 1 L capacity; 292.5 g DMTMC,7.5 g TMC and 105 mg dimethylpropanediol were used. Initial heating wasat 140° C. and the catalyst was 160 μL of 1.0M stannous octoate intoluene. After 4 hours a total of 277 g of polymer was isolated from theflask; gel permeation chromatography (GPC) using THF showed a weightaverage molecular weight of 89,000 and a dispersity of 2.4 for thepolymer peak, plus small amounts of oligomers. For spinning into fibers,the polymer was dissolved in dioxane and precipitated into water.[Sample 22, Table I]

EXAMPLE 10 Copolymerization of DMTMC and Caprolactone, 98.2:1.8

A mixture of DMTMC (26.34 g, 202 mmol), freshly distilled caprolactone(0.475 mL, 0.489 g (4.3 mmol), 2,2-dimethyl-1,3-propanediol (0.2 mmol)and stannous octoate (150 μL of 0.1M solution in toluene) was dividedbetween three polymerization tubes. The tubes were sealed under vacuumand heated at 160° C. overnight. The resulting polymers were combined,dissolved in tetrahydrofuran and precipitated into water. Yield: 38.8 g(87%). Weight average molecular weight=89,000 by GPC (THF). [Sample 29,Table II]

EXAMPLE 11 Poly(DMTMC co Caprolactone)

In an oven-dried, silanized 1 L resin flask were combined DMTMC (313.7g, 2.41 mol), distilled caprolactone (5.62 g, 49 mmol) and2,2-dimethyl-1,3-propanediol (63 mg, 0.60 mmol). After purging withargon the flask was heated to 160° C. in an oil bath; when the mixturehad become homogeneous, stannous octoate (155 μL of a 1.0M solution intoluene) was added. The mixture gradually became very thick; stirringwas discontinued after 2.5 h and the reaction was stopped after anadditional 3.5 h. The polymer was combined with those from two smallerruns, dissolved in tetrahydrofuran and precipitated into water. Yield:650 g (92%). Weight average molecular weight=89,300 by GPC (THF).[Sample 30, Table II]

EXAMPLE 12

A series of copolymers of DMTMC with varying amounts of TMC (Tables I,III) and lactides, or caprolactone (Tables II, III) were evaluated.Certain of these were spun into approximately 70 denier filament. Thesepolycarbonate copolymers could be melt spun easily in the temperaturerange 150° to 190° C. with good melt stability as indicated at aconstant melt viscosity. Drawn samples, e.g., 4A and 4B (Table III),showed satisfactory fiber tensile strength properties for fabric andhollow fiber or tubular applications as nerve channels.

EXAMPLE 13

A higher molecular weight polycarbonate resin with reduced viscosity 1.1of DMTMC and TMC (97.5:2.5) was extruded similarly as Example 12, butwith a melt temperature of 195° C. The 0.030 inch die used had an exitmelt velocity of 0.3 ft/min. and taken up at about 30 ft/min. The fiberscontinued on to a set of draw godets and are subjected to increase indraw ratio. The test results, 15A to 15E (Table III), show good fiberproperties for many fabric and hollow tube applications.

EXAMPLE 14

A copolymer of DMTMC and caprolactone of 98.2:1.8 weight ratio (Sample29, Table II) was spun as in Example 12. Fibers from a number of drawratios showed good tensile and hollow fiber or tube properties (seeExample 29 A-D in Table III).

EXAMPLE 15

A sample of a 300 g batch of a copolymer of DMTMC with TMC (97.5 to 2.5wt. %) was prepared to provide information on conditions for spinningmultifilament yarn. The material was melt spun as in Example 12 using amelt temperature of 180° C. The fibers were then drawn to yield tensileproperties listed in Table III as Sample 22. Satisfactory properties forfabric and hollow fiber or tubing applications are indicated.

EXAMPLE 16

Polycarbonate polymer recovered from Example 15 dissolved andreprecipitated was melt spun at 180° C. with a lower melt draw down andoriented to give satisfactory fiber properties listed as Sample 22A inTable III.

                                      TABLE I                                     __________________________________________________________________________    RANDOM COPOLYMERS OF DMTMC (D) AND TMC (T)                                         D:T                                                                      Sample                                                                             Weight                                                                            Method of                                                                           Quantity   Reduced                                                                            GPC Main Peak                                                                            GPC Overall                         Number                                                                             Ratio                                                                             Synthesis                                                                           Isolated                                                                           Yield (%)                                                                           Viscosity                                                                          Wt Av MW                                                                             Disp.                                                                             Wt Av MW                                                                             Disp.                        __________________________________________________________________________     1   95:5                                                                              Example 7                                                                           11.3 g                                                                             79    0.76                                                 2   95:5                                                                              Example 7                                                                            9.3 g                                                                             62    0.77                                                 3   97.5:2.5                                                                          Example 7                                                                           11.9 g                                                                             83    0.66                                                 4   97.5:2.5                                                                          Example 7                                                                           24.0 g                                                                             82    0.53                                                 5   97.5:2.5                                                                          Example 7                                                                           24.3 g                                                                             82    0.57                                                 6   97.5:2.5                                                                          Example 7                                                                           24.0 g                                                                             80    0.71                                                 7   97.5:2.5                                                                          Example 7                                                                           37.5 g                                                                             82    4.9                                                  8   97.5:2.5                                                                          Example 7                                                                           48.5 g                                                                             83    5.6                                                  9   97.5:2.5                                                                          Example 7                                                                           13.1 g                                                                             87    0.68                                                10   97.5:2.5                                                                          Example 8                                                                           24.4 g                                                                             81    0.80                                                11   97.5:2.5                                                                          Example 7                                                                           26.6 g                                                                             89    0.83                                                12   25:75                                                                             Example 7                                                                            7.8 g                                                                             89    0.86                                                13   97.5:2.5                                                                          Example 8                                                                           25.0 g                                                                             83    0.38                                                14   97.5:2.5                                                                          Example 7                                                                           10.4 g                                                                             87    1.46        150,000                                                                           18.80                               15   97.5:2.5                                                                          Example 7                                                                           10.4 g                                                                             87    1.10        115,000                                                                            7.93                               16   97.5:2.5                                                                          Example 8                                                                            5.1 g                                                                             85    0.91 64,300 3.10                                                                              62,000 10.20                        17   97.5:2.5                                                                          Example 7                                                                            5.3 g                                                                             88    1.30                                                18   97.5:2.5                                                                          Example 9                                                                           90.0 g                                                                             90    0.43 35,100 4.00                                    19   97.5:2.5                                                                          Example 7                                                                            8.3 g                                                                             83         62,500 2.88                                                                              80,500 13.40                        20   97.5:2.5                                                                          Example 9                                                                           90.0 g                                                                             90         85,600 4.36                                                                              86,700 29.30                        21   97.5:2.5                                                                          Example 9                                                                            282 g                                                                             94         142,000                                                                              3.57                                                                              127,000                                                                              37.60                        22   97.5:2.5                                                                          Example 9                                                                            277 g                                                                             92         88,700 2.38                                                                              82,500 17.80                        23   97.5:2.5                                                                          Example 9                                                                            291 g                                                                             97         113,000                                                                              3.60                                                                              108,000                                                                              18.40                        24   96.8:3.2                                                                          Example 7                                                                            9.8 g                                                                             94         257,000                                                                              3.48                                                                              257,000                                                                              28.20                        25   56.0:44                                                                           Example 7                                                                            8.6 g                                                                             87         148,000                                                                              2.06                                                                              148,600                                                                               2.07                        26   30.0:70                                                                           Example 7                                                                            6.6 g                                                                             73         41,800 2.00                                                                              41,800  2.01                        27   79.0:21                                                                           Example 7                                                                            6.4 g                                                                             94         202,360                                                                              3.16                                                                              219,000                                                                              34.60                        __________________________________________________________________________

                                      TABLE II                                    __________________________________________________________________________    RANDOM COPOLYMERS OF DMTMC (D)/CAPROLACTONE (CL) AND                          DMTMC (D)/d,1-LACTIDE                                                         Sample                                                                             D:CL Method of                                                                           Quantity   GPC Main Peak                                                                           GPC Overall                              Number                                                                             Ratio                                                                              Synthesis                                                                           Isolated                                                                           Yield (%)                                                                           Wt- Av- MW                                                                           Disp.                                                                            Wt- Av- MW                                                                           Disp.                             __________________________________________________________________________    27   98.2:1.8                                                                           Example 11                                                                          54.3 g                                                                             84    46,500 2.03                                        28   98.2:1.8                                                                           Example 11                                                                          62.0 g                                                                             95    124,000                                                                              2.50                                                                             150,000                                                                              16.30                             29   98.2:1.8                                                                           Example 10                                                                          38.8 g                                                                             87    99,500 1.34                                                                             89,000 29.53                             30   98.2:1.8                                                                           Example 11                                                                           650 g                                                                             92    91,500 2.42                                                                             89,300 4.79                              31   95.6:4.4                                                                           Example 10                                                                           9.4 g                                                                             95    132,000                                                                              2.36                                                                             156,000                                                                              11.50                             32   77.4:22.6                                                                          Example 10                                                                           9.6 g                                                                             96    104,100                                                                              1.63                                                                             170,200                                                                              2.85                              33   53.3:46.7                                                                          Example 10                                                                           8.8 g                                                                             93    14,800 2.06                                                                             14,900 2.07                              34   91.1:8.9                                                                           Example 10                                                                           8.3 g                                                                             88    10,100 2.39                                                                             88,900 29.50                             35   87.8:12.2*                                                                         Example 10                                                                           8.6 g                                                                             86    88,900 2.54                                                                             87,000 6.65                              __________________________________________________________________________     *87.8 = D:12.2 = d,1Lactide                                              

GENERAL PROCEDURES FOR LARGE SCALE BIOPOLYMER SPINNING

Random copolymers of these biopolymers such as DMTMC/TMC and DMTMC/CLwere spun using the following equipment and procedures:

Dry polymer was charged into a hopper of a Braebender 3/4 inch extruderequipped with two adjustable electrically heated zones and a heatedblock assembly consisting of an electrically heated metal block and No.2 Zenith gear pump. The spinnerette consisted of a stainless steel (316)die, containing 8 holes, 0.021" diameter and a 200 mesh screen pack.

Feed rate, extrusion temperatures and pressures are presented inExamples 17 and 18.

The filaments were air quenched and taken up on a constant speed godetset at 1448 ft/min. The second godet was set at 2854 ft/min. whichresulted in a draw ratio of 2:1. Yarn haul off was made using a Leesonawinder.

EXAMPLE 17 Run Parameters

Material: 97.5% DMTMC--2.5% TMC, Random copolymer, Samples 21-23 (TableI).

Extruder:--3/4" Braebenders

Heat:

Zone 1 (feed)--200° C.

Zone 2 (metering)--212° C.

Zone 3 (die and block)--215° C.

Screen Pack--200 mesh

Die 8 hole--0.021" diameter

Screw RPM--6

Pump RPM in percent--22

Pressure barrel--1200 psi

Pressure die--600 psi

Take up:

Roll 1/temperature--1448 ft/min. at R.T.

Roll 2/temperature--2854 ft/min. at R.T.

Final thruput--0.4 gms/hole/min.

Final draw ratio--2:1

Denier--5 DPF towed to 200/40

EXAMPLE 18 Run Parameters

Material: 98.2% DMTMC--1.8% CL, Random copolymer, Sample 30 (Table II)

Extruder:--3/4" Braebender

Heat:

Zone 1 (feed)--190° C.

Zone 2 (metering)--200° C.

Zone 3 (die and block)--210° C.

Screen Pack--200 mesh

Die 8 hole--0.021" diameter

Screw RPM--.sup.˜ 6 Pump RPM in percent--.sup.˜ 22

Pressure barrel--1200 psi

Pressure die--600 psi

Take up:

Roll 1/temperature--1448 ft/min. at R.T.

Roll 2/temperature--2854 ft/min. at R.T.

Final thruput--0.4 gms/hole/min.

Final draw ratio--2:1

Denier--5 DPF towed to 200/40

                  TABLE III                                                       ______________________________________                                        Fiber Mechanical Properties                                                                                        Ultimate                                               Tensile Modulus                                                                            Tensile   Elongation                               Sample                                                                              Denier  (g/d)        Strength (g/d)                                                                          (%)                                      ______________________________________                                        4A    10      90           5.5       16                                       4B    13      70           3.4       24                                       10    198     22           0.3        7                                       15A   33      37           1.4       24                                       15B   19      41           1.5       29                                       15C   17      51           2.5       26                                       15D   17      57           2.7       23                                       15E    4      82           4.0       17                                       29A   13      45           3.4       50                                       29B   13      43           3.7       53                                       29C   13      50           3.7       49                                       29D   11      88           4.4       20                                       22    12      62           4.5       27                                       22A   48      45           4.8       30                                       24    29      43           2.9       43                                       ______________________________________                                    

EXAMPLE 19 Copolymerization of DMTMC and TMC in Xylene Solution

In an oven-dried 100 mL resin flask DMTMC (7.81 g, 60 mmol), TMC (6.13g, 60 mmol) and dimethylpropanediol (3 mg) were combined. The flask wasevacuated to 0.1 mm Hg for ten minutes, then filled with dry argon.Xylene (15 mL), dried by distilling from sodium metal, was added to theflask by syringe, then the flask was immersed in an oil bath at 150° C.After stirring for five minutes, tin octoate (25 μL of a 1.0M solutionin toluene) was added. The solution became very viscous over a two hourperiod; a sample (ca. 200 mg) was taken and diluted with 5 mLtetrahydrofuran. Analysis by GPC showed a weight average molecularweight of 142,000. The polymer solution was precipitated into methanol,the polymer washed with methanol and dried. NMR analysis of theprecipitated sample showed a TMC content of 51% and DMTMC content of49%. From the carbonyl carbon region of the 100 MHz carbon spectrum, itwas determined that the carbonate groups of the polymer consisted of 27%DMTMC-DMTMC linkages, 28% TMC-TMC linkages and 45% DMTMC-TMC linkages.

EXAMPLE 20 ABA Block copolymer of 5,5-Dimethyl-1,3-dioxan-2-one (DMTMC)and Caprolactone (CL); B=1:1 DMTMC:CL, A=DMTMC, A:B=80:20

An oven-dried, silanized glass 150 mL resin flask was equipped withmechanical stirrer and a teflon paddle, argon inlet, a serum cap on oneport, and a glass stopper on the remaining port. To the flask were addedfreshly dried and purified DMTMC (4.15 g, 31.9 mmol), caprolactone (3.64g, 31.9 mmol), and 2,2-dimethylpropanediol (7.5 mg, 0.072 mmol). Theflask was evacuated and filled with argon several times, then immersedin an oil bath at 160° C. Stirring was initiated, and after 5 minutes,25 μL of a 1.0M solution of stannous octoate in toluene, the catalystsolution, was added. Noticeable thickening occurred in about 20 minutes;after 1.5 hours, the oil bath was lowered and the flask was evacuatedbriefly to remove some of the unreacted monomers that had condensed onthe upper part of the flask. Heating was resumed and DMTMC (6.64 g, 51mmol) was added, followed by an additional 25 μL of the catalystsolution. After an additional 10 minutes, more DMTMC (26.57 g, 204.2mmol) was added and the mixture stirred with continued heating at 160°C. In about 30 minutes, the mixture became too thick to be stirred, butheating was continued for an additional hour, when the polymerizationwas terminated.

The viscous polymer was scooped out of the flask (37.8 g recovery),dissolved in dioxane (300 mL), and precipitated in a blender into water(1200 mL). The polymer was then washed twice in the blender with water,filtered and dried in vacuum at 45° C. overnight. Yield: 32.9 g (80%).Weight average molecular weight=121,000 by GPC (THF solvent). [Sample 3,Table IV]

EXAMPLE 21 ABA Block Copolymer of DMTMC and Caprolactone (CL); B=1:1DMTMC:CL, A=DMTMC, A:B=70:30

A polymerization similar to Example 20 was carried out in a 1 literresin flask. The first (B-block) stage employed 39.04 g (300 mmol)DMTMC, 34.24 g (300 mmol) caprolactone, 30 mg (0.29 mmol)2,2-dimethylpropanediol, and 150 μL of 1M stannous octoate in toluene.After 2 hours heating at 160° C., the reactor was evacuated briefly andall of the remaining DMTMC (182.2 g, 1400 mmol) was added at once. Anadditional 150 μL of catalyst solution was added and stirring continuedfor 2.5 hours until the polymer became too viscous to stir. Heating at160° C. was continued overnight, then the polymer was removed from theflask, dissolved in 2.5 L dioxane and precipitated in batched into water(ca 10L). After washing and drying as before, the polymer weighed 226 g(89%). Weight average molecular weight=110,000 by GPC (THF);caprolactone content by ¹ H NMR= 17% (theory 15%). [Sample 8, Table IV]

Similarly, other examples of these block copolymers of DMTMC andcaprolactone were prepared and reported in Table IV.

EXAMPLE 22 ABA Block Copolymer of DMTMC and Trimethylene Carbonate(TMC); B=TMC, A=DMTMC, A:B=80:20

A polymer was prepared as in Example 20, except that the initial chargeconsisted of TMC (6.12 g, 60 mmol) and 2,2-dimethylpropanediol (10.3 mg,0.1 mmol). The flask was immersed in an oil bath at 160°, then afterfive minutes 25 μL of 1M stannous octoate was added. In 30 minutes theTMC had polymerized to a viscous material, this was sampled and thenDMTMC (31.12 g, 240 mmol) was added all at once. The poly(TMC)prepolymer gradually dissolved in the DMTMC and the mixture becamehomogeneous and eventually very viscous. After a total time of 3.5hours, the reaction was stopped and worked up as in Example 20. Yield:27.7 g (74%). Trimethylene carbonate content by ¹ H NMR=23.6% (theory20%). Weight average molecular weight by GPC (THF) of prepolymer=37,000,of final polymer=105,000. Differential scanning calorimetry (DSC) of thefinal polymer showed a glass transition temperature (Tg) of 0° C. and amelting temperature (Tm) of 71° C. [Sample 20, Table V].

Similarly, other examples of such block copolymers of DMTMC and TMC orDMTMC and TMC/lactides were prepared and reported in Table V.

EXAMPLE 23 Block Copolymerization of DMTMC and TMC in Xylene Solution

In an oven-dried 100 mL resin flask were combined DMTMC (7.81 g, 60mmol), TMC (6.13 g, 60 mmol) and dimethylpropanediol (3 mg). The flaskwas evacuated to 0.1 mm Hg for ten minutes, then filled with dry argon.Xylene (15 mL), dried by distilling from sodium metal, was added to theflask by syringe, then the flask was immersed in an oil bath at 150° C.After stirring for five minutes, tin octoate (25 μL of a 1.0M solutionin toluene) was added. The solution became very viscous over a two hourperiod; a sample (ca. 200 mg.) was taken and diluted with 5 mL THF.Analysis by GPC showed a weight average molecular weight of 142,000. Thesolution was precipitated into methanol. The polymer was washed withmethanol and dried. NMR analysis of the precipitated sample showed a TMCcontent of 51% and DMTMC content of 49%. From the carbonyl carbon regionof the 100 MHz carbon spectum, it was determined that the carbonategroups of the polymer consisted of 27% DMTMC-DMTMC linkages, 28% TMC-TMClinkages and 45% DMTMC-TMC linkages.

Additional DMTMC (10.41 g, 80 mmol) was added to the flask and themixture stirred at 150° C. for an additional 3.5 hours. The polymer wasdissolved in 350 mL dioxane, precipitated into methanol (1100 mL),washed with additional methanol and dried. Yield: 19.0 g (78%). Weightaverage molecular weight=168,000 by GPC (THF). TMC content=32% by protonNMR (theory=30%). The carbonyl region of the spectrum shows 48%DMTMC-DMTMC linkages, 36% DMTMC-TMC linkages and 16% TMC-TMC linkages;calculated values assuming only DMTMC-DMTMC linkages are formed in thesecond stage: 50% DMTMC-DMTMC, 31% DMTMC-TMC, and 19% TMC-TMC.

EXAMPLE 24

The block copolymer of DMTMC and caprolactone listed as Sample 2 inTable IV was melt extruded into monofilament fiber at 195° C. The fiberswere drawn at room temperature and good fiber characteristics wereobtained as documented in Table IV as samples 2A-2G.

EXAMPLE 25

The block copolymer of DMTMC and caprolactone listed as Sample 3 inTable IV was melt extruded and moderately drawn to limit the tensilemodulus. Low modulus fibers of good strength and high elongations wereachieved as shown in Table VI as entries 3A-3B.

EXAMPLE 26

The block copolymer of DMTMC and caprolactone listed as Sample 5 inTable IV was melt spun and drawn at room temperature at a number of lowdraw ratios to limit the modulus. Good fiber strengths at these lowmoduli were achieved as shown in Table VI as 5A-5E.

EXAMPLE 27

Fiber 5D from Table VI was heat set on a heated block at 74°-77° C. at100 ft/min under a 2% overdraft and at draw ratios of 1.06, 1.22, 1.3and 1.42. These fibers are listed as 5D-1 through 5D-5, respectively, inTable VI.

                                      TABLE IV                                    __________________________________________________________________________    ABA BLOCK COPOLYMERS OF CAPROLACTONE (CL)                                     AND DIMETHYLTRIMETHYLENE CARBONATE (DMTMC)                                    Sample                                                                             A    B        A:B Quantity   GPC Main Peak                                                                           GPC Overall                       Number                                                                             Block                                                                              Block    Ratio                                                                             Isolated                                                                           Yield (%)                                                                           Wt Av MW                                                                             Disp.                                                                            Wt Av MW                                                                             Disp.                      __________________________________________________________________________    1    DMTMC                                                                              DMTMC:CL 3:1                                                                           70:30                                                                              20.0 g                                                                            65     47,300                                                                              2.55                                                                              50,400                                                                              4.63                       2    DMTMC                                                                              DMTMC:CL 4:1                                                                           85:15                                                                              41.3 g                                                                            87    118,000                                                                              3.70                                                                             181,000                                                                              47.60                      3    DMTMC                                                                              DMTMC:CL 1:1                                                                           80:20                                                                              32.9 g                                                                            80    140,000                                                                              4.20                                                                             121,000                                                                              33.60                      4    DMTMC                                                                              DMTMC:CL 3:1                                                                           77:23                                                                              33.4 g                                                                            81     92,000                                                                              3.50                                                                              93,400                                                                              13.15                      5    DMTMC                                                                              DMTMC:CL 1:1                                                                           70:30                                                                              32.1 g                                                                            79    132,000                                                                              2.80                                                                             152,000                                                                              14.30                      6    DMTMC                                                                              DMTMC:CL 1:1                                                                           70:30                                                                             210.4 g                                                                            82     67,100                                                                              1.90                                                                              67,100                                                                              1.90                       7    DMTMC                                                                              DMTMC:CL 1:1                                                                           70:30                                                                             223.7 g                                                                            88     83,800                                                                              1.68                                                                              83,800                                                                              1.68                       8    DMTMC                                                                              DMTMC:CL 1:1                                                                           70:30                                                                             226.6 g                                                                            89    110,000                                                                              2.90                                                                             113,000                                                                              19.50                      9    DMTMC                                                                              DMTMC:CL 1:1                                                                           70:30                                                                             Blended     89,600                                                                              2.90                                                                             112,500                                                                              16.50                      __________________________________________________________________________

                                      TABLE V                                     __________________________________________________________________________    ABA BLOCK COPOLYMERS OF                                                       TRIMETHYLENE CARBONATE (TMC), d,1-lactic acid (LA)                            DIMETHYLTRIMETHYLENE CARBONATE (DMTMC)                                        __________________________________________________________________________    Sample A      B         A:B  Quantity                                         Number Block  Block     Ratio                                                                              Isolated                                                                           Yield (%)                                   __________________________________________________________________________    10     DMTMC  TMC:DMTMC 1:1                                                                           25:75                                                                              33.6 g                                                                             88                                          11     DMTMC  TMC:DMTMC 1:1                                                                           35:65                                                                              33.4 g                                                                             75                                           12*   DMTMC  TMC:DMTMC 1:1                                                                           65:35                                                                              35.8 g                                                                             80                                          13     DMTMC  TMC:DMTMC 1:1                                                                           40:60                                                                              36.0 g                                                                             82                                          14     DMTMC  TMC:DMTMC 1:1                                                                           50:50                                                                              30.5 g                                                                             83                                          15     DMTMC  TMC:d,1-LA 1:1                                                                          80:20                                                                              29.8 g                                                                             82                                          16     DMTMC  TMC:DMTMC 1:1                                                                           60:40                                                                              17.3 g                                                                             46                                          17     DMTMC  TMC:DMTMC 1:1                                                                           60:40                                                                              29.9 g                                                                             80                                          18     DMTMC  TMC       60:40                                                                              30.0 g                                                                             84                                          19     DMTMC  TMC       80:20                                                                              27.7 g                                                                             74                                          20     DMTMC  TMC       70:30                                                                              30.3 g                                                                             83                                          __________________________________________________________________________    Sample                                                                             GPC Main Peak                                                                           GPC Overall        TMC by NMR                                  Number                                                                             Wt Av MW                                                                             Disp.                                                                            Wt Av MW                                                                             Disp.                                                                            Tg   Tm  % (Theory)                                  __________________________________________________________________________    10   48,400 6.20                                                                             48,500 3.20            (38)                                    11   112,000                                                                              8.06                                                                             92,000 2.30            (33)                                    12   124,000                                                                              4.34                                                                             159,000                                                                              5.48            (18)                                    13   196,000                                                                              4.90                                                                             194,000                                                                              20.80           (30)                                    14   64,500 3.60                                                                             65,100 22.00           (25)                                    15   102,000                                                                              2.40                                                                             101,700                                                                              4.28            (10)                                    16   64,000 4.70                                                                             83,100 22.40                                                                            -2° C.                                                                      71° C.                                                                     31.6                                                                              (20)                                    17   87,000 4.80                                                                             99,000 23.00                                                                             3° C.                                                                      60° C.                                                                     22.0                                                                              (20)                                    18   53,100 3.36                                                                             61,800 10.50                                                                            -12° C.                                                                         44.0                                                                              (40)                                    19   113,000                                                                              3.60                                                                             105,000                                                                              22.60                                                                             0° C.                                                                      71° C.                                                                     23.6                                                                              (20)                                    20   51,500 4.10                                                                             84,800 24.30                                                                            -3° C.                                                                      59° C.                                                                     31  (30)                                    __________________________________________________________________________     *Sample 12 is a BAB block copolymer                                      

                  TABLE VI                                                        ______________________________________                                        Tensile properties of Monofilament Fiber (tested at 23° C., 50%        RH at 100% extension rate with 5 inch gauge length yarn samples               average of ten or more measurements).                                                       Tensile     Tensile                                                           Modulus     Strength Ultimate                                   Sample                                                                              Denier  grams/denier                                                                              grams/denier                                                                           Elongation %                               ______________________________________                                        2A    100     26          1.3      244                                        2B    12      83          4.9      19                                         2C    14      90          4.8      24                                         2D    18      98          3.6      34                                         2E    15      77          3.9      25                                         2F    12      89          4.6      16                                         2G    16      76          4.1      38                                         3A    74      26          3.6      66                                         3B    60      31          4.2      61                                         5A    49      33          4.6      30                                         5B    59      13          3.9      66                                         5C    53      22          4.6      54                                         5D    55      10          4.0      49                                         5E    46      19          4.4      54                                         5E-1  52       9          4.3      57                                         5E-2  48      15          4.4      49                                         5E-3  42      30          5.2      34                                         5E-4  41      26          5.2      31                                         5E-5  47      32          5.2      23                                         ______________________________________                                    

EXAMPLE 28 ABA Block Copolymer of Trimethylene Carbonate (TMC),d,l-lactic Acid (d,l-LA) and l-lactic Acid (l-LA)

An oven-dried, silanized glass 100 mL resin flask was equipped withmechanical stirrer and a glass paddle, argon inlet, a serum cap on oneport, and a glass stopper on the remaining port. To the flask were addedfreshly dried and purified TMC (19.80 g, 194 mmol), d,l-Lactide (2.20 g,15.3 mmol), and 2,2-dimethyl-1-3-propanediol (27 mg, 0.26 mmol). Theflask was evacuated and filled with argon several times, then immersedin an oil bath at 150° C. Stirring was initiated, and after 5 minutes,40 μL of a 1.0M solution of stannous octoate in toluene was added.

After one hour, a sample of the viscous polymer was removed andl-Lactide (9.43 g, 65.4 mmol) was added through one port. Stirring wasstopped after one hr., then heating stopped after an additional hr. Thepolymer was removed from the flask, dissolved in tetrahydrofuran (250mL), precipitated into methanol (750 mL), and dried under vacuum at 50°C. Yield: 23.2 g (74%). Weight average molecular weight (relative topolysytrene standards) of the prepolymer=57,000; of the finalpolymer=107,000. Proton NMR analysis of the final polymer shows a TMCcontent of 50 mole percent (theoretical=55%). From the methine region ofthe proton NMR, one can estimate that about 74% of the lactic acid unitsare connected to other lactic acid units, compared to a theoreticalvalue of 89.5% for a totally random B block and a totally homopolymer Ablock.

Similarly, two experiments were performed using this method to prepareother such block copolymers:

    __________________________________________________________________________    ABA BLOCK COPOLYMERS OF TRIMETHYLENE CARBONATE (TMC),                         d, 1-lactic acid (d,1-LA) and 1-lactic acid (1-LA)                                                                                      % TMC               Sample                                                                            A   B       A:B Quantity                                                                           Yield                                                                             GPC Main Peak                                                                           GPC Overall        by NMR              No. Block                                                                             Block   Ratio                                                                             Isolated                                                                           (%) Wt Av MW                                                                             Disp.                                                                            Wt Av MW                                                                             Disp.                                                                            Tg   Tm  (Theory)            __________________________________________________________________________    1   1-LA                                                                              TMC:d,1-LA                                                                            30:70                                                                             21.2 g                                                                             78  94,000 2.64                                                                             120,900                                                                              24.8                                                                              -5° C.                                                                     150°                                                                       63 (63)                     9:1                                                                   2   1-LA                                                                              TMC:d,1-LA                                                                            36:64                                                                             22.0 g                                                                             72  86,800 1.72                                                                              80,800                                                                               1.72                                                                            -10° C.                                                                     156°                                                                       56 (55)                     7.3:1                                                                 __________________________________________________________________________

EXAMPLE 29 Completely Bioresorbable Graft-Fabrication

1. Random copolymer compositions: Fiber "A"=97.5% DMTMC/2.5% TMC andFiber "B"=98.2% DMTMC/1.8% caprolactone.

2. Fibers "A" and "B": as obtained from Examples 17 and 18.

3. Weaving: The 200 denier fiber was twisted 7.125 turn/inch whenrepackaged, to be used for the filling (horizontal) and wrap (vertical)construction to keep the monofilaments together. The fabrics were aplain weave tube with both warp and fill directions having the samefiber, at a construction of 120 total body ends by 120 picks per inch(that is a perfect square, tight weave). The total circumferences were18.8 and 25.2 mm for each of the fibers used, which correspond to 6 and8 mm diameter respectively. Some obviously defective areas were foundfrom time to time due to slight changes of tension on the fill bobbin,and also due to the knots in the towed fiber.

4. The flat fabric was heat-set between 60° to 90° C. to round (crosssection) with a glass mandrel and cleaned with 0.05% Triton X-100detergent in 50% ethanol-water, then rinsed 6 times with water, andfinally rinsed with absolute ethanol. The operation was performed insidea class 100 laminar flow hood up-to and including packaging of thedevice in sterilization pouches.

5. Room temperature ethylene oxide was used to sterilize thesecompletely bioresorbable vascular grafts.

6. The water permeation rates at 120 mm Hg pressure after heat-set ofsuch prostheses were below 500 cc/cm² /minute. They were implantedbilaterally in sheep as carotid replacements without preclotting. Nocomplications resulted.

Likewise, yarns made from the block copolymers such as those describedand used in Example 40 can also be similarly fabricated intobioresorbable grafts.

EXAMPLE 30 Completely Bioresorbable Crimped and Coated Graft

1. Totally bioresorbable 6 mm vascular grafts were woven from Fiber "A"and "B" as described in Example 29, sections 1 to 3. Crimping accordingto the general method of Jekel (U.S. Pat. No. 3,337,673) was used. Thus,the spacer was provided by a cotton string helically wound on the fabricgraft body with a glass mandrel inserted into the lumen. Crimp-shape wasformed by slowly forcing the two ends of the graft towards the middle.The crimping can be set to as small as 0.5 millimeter up and 0.1 to 0.2mm down so that the internal surface appears to be almost smooth butstill resist kinking. After heat-setting, cleaning was done according tosection 4 of Example 29.

A solution containing 2 to 3% coating polymer, e.g., the randomcopolymer of 91% TMC--9% l-lactide, was made with solvent dimethylsulfoxide (DMSO). The clean bioresorbable graft was dipped into saidsolution six dips, inverting between each dip, to yield a 10% weightgain. In another example, when a 4.5% coating solution was used, 25%weight gain was obtained after nine dips. The dipping was performedinside a Class 100 laminar flow hood.

2. Standard room temperature cycle ethylene oxide was used to sterilizethese completely bioresorbable coated and crimped vascular grafts.

3. The water permeation rates at 120 mm Hg pressure of such prostheseswere about 400 cc/cm² -minute. They were implanted bilaterally in sheepas carotid replacements without preclotting. No complication resulted.The patency rate at 12-week stands at 100% (6 out of 6 grafts) for these6 mm, totally bioresorbable, crimped and coated vascular grafts.

EXAMPLE 31

Four 8 centimeter long pieces of human-implantable grade, crimped USCISauvage Bionit, vascular grafts manufactured by C. R. Bard, having a sixmillimeter diameter, were ultrasonicated with 0.05% Triton X-100 in 1:1alcohol/water for sixty minutes at room temperature. The vascularprotheses were then rinsed several times with deionized water, followedby two rinses with 95% ethanol and drying in a laminar blow hoodequipped with high efficiency air filters. The dried vascular graftswere immersed into a solution of 1.40 grams of double-precipitated polyTMC (approx. 91,200 Daltons weight average molecular weight) in 140 mLof tetrahydrofuran, THF. The vascular grafts were inverted after eachdip, allowed to dry, and weighed until the desirable weight gains wereattained. A total of seven dips were performed for a 25% weight-gain.The dipping and packaging were performed inside the laminar flow hood.The protheses were subjected to room temperature ethylene oxidesterilization. The water permeation rate decreased from 1,500 to below200 cc/cm² min. after the coating.

Under anethesia, light anticoagulation (during implantation) and sterileoperating room conditions, two vascular grafts were implanted byend-to-end anastomoses without preclotting into both the left and rightexternal carotid arteries of each of the two mixed adult domestic femalesheep weighing approx. 50 kilograms. After twelve weeks of indwelling,all grafts were opened to blood flow when each animal was anticoagulatedand sacrificed by euthanasia. The grafts were excised. All fourrecovered grafts with bioresorbable coatings were patent and displayed athin, smooth pseudoneointimal layer on its luminal blood contactingsurface.

Control Experiment. For comparison, the same procedure was performedwith the Sauvage Bionit graft as received without coating. However, thegrafts were preclotted just prior to insertion, a standard procedureused to diminish bleeding as suggested by the manufacturer. The patencyrate was 15 out of 18 (83.33%). All luminar surfaces of the implantswere covered with a much thicker layer of internal capsule and redthrombus as compared to the coated grafts described above.

EXAMPLE 32

Under the same operative and coating procedures described Example 31, atotal of eight 8 centimeter long, six millimeter diameter Sauvage Bionitvascular grafts were coated with 25% weight-gain of a random copolymerof 91% TMC and 9% L-lactide (approx. 87,000 Dalton weight average MW)were implanted as bilateral carotid replacement in four adult femalesheep.

After seven weeks, one of the four sheep was electively terminated andboth grafts were patent and displayed pearllike neointimal surfaces. Theremaining three animals were kept to twelve weeks and electivelyterminated so as to be able to be compared to the control described inExample 31. All six excised grafts were patent and the blood contactingsurfaces displayed smooth translucent pseudoneointimal layers.

EXAMPLE 33

Similar to Example 32, four similar eight centimeter long six millimeterdiameter Sauvage Bionit vascular graft with the same coating polymer but50% weight gain were implanted in two adult sheep as bilateral carotidreplacements. One was electively terminated at seven weeks and the otherat twelve weeks. All four excised grafts were patent at termination withpearl-like blood contacting surfaces.

EXAMPLE 34

Fibers extruded from Example 17 (that is random copolymer of 97.5% DMTMCand 2.5% TMC by weight) were towed to 180 denier and woven into sixmillimeter tubular fabric with 120 body ends per inch by 120 picks perinch. The fabric was crimped by first wrapping a cotton thread spirallyaround the tubular fabric supported with a pyrex glass rod as a mendrel,then compressed and heat-set at approx. 80° C. The experimental graftswere cleaned as previously described. The grafts were further coatedwith the random copolymer of 91% TMC and 9% L-lactide from a 2 wt %solution in dimethylsulfoxide which dissolved the coating copolymer butnot the fabric fiber. The water permeation rates dropped from 300 cc/cm²min. to about zero after coating. A total of fourteen eight centimeterlong six millimeter diameter completely bioresorbable vascular grafts,crimped and coated with 10% wt-gain, were implanted as bilateral carotidreplacements in adult sheep as described in Example 31. One sheep diedacutely (never recovered from anesthesia) for reasons unrelated to thegrafts, as both grafts and the suture-lines were all intact. Fiveanimals were kept to twelve weeks post operation and electivelyterminated. All ten excised vascular grafts were patent. The last animalwas electively terminated after 24 weeks and both of the excised graftswere patent.

EXAMPLE 35

As in Example 34, six mm diameter vascular grafts were woven from yarnsextruded from random copolymer with 95.6% DMTMC and 4.4% caprolactone.It was crimped, cleaned, coated and sterilized as described. A pair ofsuch grafts, with 10% coating (copolymer of 91% TMC and 9% L-lactide)were implanted under sterile conditions, as described, into an adultsheep as bilateral carotid replacements. After eight weeks indwelling,the animal was electively terminated and the excised grafts were patentand the neointimal surfaces were thin and pearl-like.

EXAMPLE 36

Six Weavenit Dacron (Meadox Medical), crimped human implantable vasculargrafts (4 mm diameter, 4 cm in length) were coated to 10% weight-gainwith random copolymer of 91% TMC and 9% L-lactide in tetrahydrofuransolution. Water permeation rate dropped from 1,500 cc/cm² min. to 175cc/cm² min when coating was equal to 10% of the initial weight. The leakrate was considered to be tolerable without preclotting. Aftersterilization, they were implanted as carotid replacements in threemongrel dogs weighting approximately 22 kilograms each. Each dogreceived dipyridamole (25 mg) and aspirin (325 mg) beginning at 4 dayspreoperatively and continued for 2 weeks post-operatively so as tominimize the effect of sugery. All three animals were electivelyterminated at 4 weeks postoperatively (i.e., the subjects were withantiplatelet treatment for two weeks followed by two without suchtreatment). Four of the six grafts were found to be patent.

EXAMPLE 37

Similar to Example 36, four such Weavenit four millimeter diametergrafts were coated with the copolymer of 91% TMC and 9% L-lactide to 25%weight-gain. The water leakage rate dropped from 1500 cc/cm² min toalmost zero. The grafts were implanted into two mongrel dogs given thesame antiplatelet treatment for the pre- and post-operative periods. Atfour weeks post-operation, both animals were electively terminated andthe four excised grafts were found to be patent.

EXAMPLE 38

Similar to Example 37, two Weavenit four millimeter diameter vasculargrafts were coated with a homopolymer, poly TMC, to 25% wt-gain. Thewater permeation rate dropped from 150 cc/cc² min to almost zero. Thegrafts were implanted into a mongrel dog as bilateral carotidreplacements. After four weeks post-operation, the animal was electivelyterminated and both grafts were found to be patent.

EXAMPLE 39 Fabrication of Rod and Ribbon as External Support For Dacronor Bioresorbable Vascular Grafts

1. An ABA block copolymer [A:B 70:30, A=polyDMTMC, B=1:1 randomcopolymer of DMTMC:TMC] was extruded at 220° C. in the modified Instronextruder with first a 1 mm diameter die onto a clean chrome plate. Theunstretched round rodshaped extrudate was coiled on the plate. Theproduct was placed inside a laminar flow hood to allow for the copolymerto crystallize. After two days, the appearance of the rods changed fromcompletely transparent to slightly hazy. The ca. 1 mm rod was stretchedsix-fold and then was attached to a 8 cm long piece of straight Weavenitknitted Dacron 4 mm vascular graft (Meadox Medical Inc. Catalog No.07U004, Lot No. 237012) in a spiral fashion and fastened every 20° with7-0 Prolene suture. The protheses was cleaned with 0.05% Triton X 100 in50/50 water/ethanol in an ultrasonic bath for 1 hr. rinsed 6 times withdeionized water, 2 times with 95% ethanol before it was hung in alaminar flow hood to air dry. A clean and dry 4 mm OD pyrex glass rodwas inserted into the graft so that a good contact would be establishedbetween the knitted fabric and the external spiral support to enhanceadhesion when the coating solution is applied. The coating solutioncontained 2% by weight of a random copolymer of 91% trimethylenecarbonate and 9% L-lactide (wt average molecular weight=87 K) indimethyl sulfoxide. A total of eight dips were applied before the totalweight gain reached 10%. The Prolene suture was later removed. The graftdid not kink or collapse upon bending.

2. The block copolymer was similarly extruded but a die with aretangular orifice measuring 4.0 mm×1.0 mm was used. When the extrudedrod turned slightly milky white, ca. 6 inch. pieces were each stretchedsix and a half times of their original length and stabilized on a solidsurface to allow the stretched plastic to set. The final size was 2.0mm×0.5 mm. It was similarly attached to a 4 mm straight Weavenit Dacronvascular graft. The graft was also coated as before. The benefit of notkinking and collapsing was also achieved.

3. The same block copolymer was extruded in a similar fashion but thedie size was changed to 4.0 mm×0.50 mm. After aging and stretching, thefinal ribbon size was 2.0 mm×0.25 mm. It was attached to 4 mm diameterstraight Weavenit Dacron vascular graft in the same manner and coated asbefore. The prosthesis stayed open when bent, and kinking or collapsingwas avoided.

4. Similarly, the rod or ribbon can be applied to a completelybioresorbable graft since the bioresorbable yarn used to fabricate thetotally bioresorbable graft was not affected by the dimethyl sulfoxidesolvent.

EXAMPLE 40 Suture Fabrication

1. Using a 0.030" round hole die, ABA block copolymer [A:B=70:30=DMTMC:(1:1=DMTMC:TMC)] and the modified Instron as an extruder, fibers wereextruded at 220° C. and with overall draw of 5.0, 5.5 and 5.8. Thefibers were stored for 72 hrs., then further drawn five to one (whichwas close to the maximum) and held at that length for 72 hrs. The sizeof the final fiber met the U.S.P. specification for 6-0 syntheticsuture.

2. Using a 0.060" round die and an ABA block copolymer [A:B=70:30=DMTMC:(1:1=DMTMC:TMC)] and the modified Instron as an extruder, fibers wereextruded at 220° C. with overall draw at 40, 6.22 and 6.66. The fiberswere stored for 48 hrs in the laminar flow hood. The fibers which had a6.66 draw were further drawn five to one (which was the maximum) andheld to that length for 72 hrs. The size of the final fiber met theU.S.P. specification for 5-0 synthetic suture.

3. Sutures and fibers from previous examples can also be coated,multiplyed or braided to be used in areas where higher mechanicalstrength, softer texture or better knot holding capability is desired.

EXAMPLE 41 Nerve Channel Extrusion

The fabrication of polycarbonates to nerve channels, tubes, or hollowfibers based on DMTMC with TMC or caprolactone or l-lactide with TMCtype of copolymers in an ABA or BAB triblock structure where A is aDMTMC or l-lactide hard block and B, the rubbery block, is a copolymerof DMTMC with TMC or DMTMC with caprolactone, or TMC with or withoutlactides, was evaluated using the Instron Rheometer as a ram extruderand a tube in orifice type die. The hollow fiber or tube dimensions werecontrolled by the die dimensions, differential gas pressure between theinner and outer surfaces of the tube, melt draw down and subsequentorientation processes. Range of diameters was about 0.5 to about 3 mminternal diameter, with significant wall thickness to provide rigidityand strength for implantation into an animal or human.

Dies having the outer diameters of the center tube of about 1.5 mm andorifices ranging from 2.5-3.5 mm were used without an appreciableapplied pressure differential. There was significant die swell duringextrusion which provided inner tube diameters greater than 3 mm. Otherdesirable diameters were easily achieved by drawing.

EXAMPLE 42

Sample 10 from Table V, an A-B-A block copolymer of DMTMC (A block) anda 50/50 random copolymer of DMTMC and TMC (B block) was extruded intohollow fibers or tubes ranging from 0.5 to 2 mm in diameter using atube-in-orifice die. The tubes were still somewhat tacky when dry,although they could be easily handled when wet. Tubes having 0.2 mm wallthickness for 1 mm OD would spring open when pressed together.

EXAMPLE 43

Sample 12 from Table V was B-A-B block copolymer of DMTMC (A block) anda 50/50 copolymer of DMTMC and TMC (B block). Because of its highmolecular weight and related high melt viscosity, the polymer meltfractured when extruded. Satisfactory tubes could, however, be extrudedat 220° C. The melt strength of this BAB structure was significantlylower than the A-B-A structure in Sample 11. The material also is moretacky than the ABA structure. However, tubes pinched close would reopen,indicating that a high molecular weight of the A block is desirable.Tube inner diameters of 0.5 to 3 mm were achieved.

EXAMPLE 44

An A-B-A block copolymer was made, Sample 13, Table V, where the A-blockwas DMTMC, and the B-block was a 50/50 random copolymer of DMTMC andTMC, with the B block molecular weight being the highest in this seriesof A-B-A polymers of DMTMC and TMC. This material extruded well at 180°C. and tube sizes ranging from inner diameters of 0.5 to 3 mm wasachieved. Tack was lower than previous examples, and the dry tubesreopened when pinched closed.

EXAMPLE 45 Nerve Channel Fabrication via Solution Dipping

Samples ranging from 0.5 mm I.D.×0.75 mm O.D. to 3.0 mm I.D.×3.50 mmO.D. were routinely prepared by this method for use as nerve channels.

a. Mandrel materials included, e.g., Pyrex glass tubings or rods,stainless steel (316) tubings or rods, platinum wires and tungsten wiresor rods. They were selected partly because of their higher surfaceenergy so that the polymer solution would spread evenly on theirsurfaces and partly because they were relatively inert so they can becleaned easily and reused.

b. Solvents: Usually tetrahydrofuran and a few drops methyl ethyl ketoneor methyl isobutyl ketone. Occasionally, chloroform or 1,4-dioxane wasused as the primary solvent depending on the solubility of the polymersystem.

c. Polymer solutions ranging from 1% to 15% by weight to solvent volumeratio have been used and the concentration was adjusted so that between8 to 20 dips would give the desirable wall thickness. (The rule of thumbis that the larger the diameter, the thicker the wall will be needed toavoid collapsing. Therefore, either more dips would be required or aslightly more concentrate solution could be used.)

d. Time between dips was usually ten to thirty minutes. For a fewpolymer systems, the wall contracted after overnight drying. Thus, anadditional one or two dips had to be performed the following morning,i.e., 15 to 16 hours later.

e. Molecular weight of polymer used (weight average) generally rangedfrom 10,000 to 250,000, as determined by GPC in tetrahydrofuran andcalibrated with polystyrene standards. No significant or detectablechange of molecular weight was recorded with the polycarbonates used,before and after fabrication.

f. Most of the protheses were cut to the desired lengths while still onthe mandrel. Before demandreling, the protheses were soaked in methanolor methanol/water or water for an hour in the refrigerator. This helpedto remove the protheses off the mandrel and demandreling was performedin a Class 100 laminar flow hood and handled with clean room gradegloves.

g. Sterilization was generally performed with ethylene oxide at roomtemperature.

In this manner, nerve channels from homopolymer, random or blockcopolymer were prepared.

EXAMPLE 46 Tendon and Ligament Replacement Devices

Tendon and ligament replacement devices can be fabricated from thesebiopolymer fibers by the following techniques.

A. Uniaxial towed fiber device

A bundle of well aligned fibers roughly with cross-sectional dimensionsof 5-6 mm by 0.4-0.5 mm and with a length of 45 cm are fastened onto twosurgical needles. The device is cleaned with 0.05% Trinton X-100 in 50%ethanol-water, then rinsed six times with water, and finally rinsed withabsolute alcohol. The operation is performed inside a class 100 laminarflow hood from the cleaning of the device up to and including packagingof the device in sterilization bags. Room temperature ethylene oxide isused to sterilize these devices.

The device of this size is useful for tendon or ligament replacements insmall animals, e.g., the Achilles tendon in rabbits.

B. Coated uniaxial towed fiber devices

A bundle of 44 yarns of Fiber F (a 220 denier yarn made from a 5 denierper filament fiber with tensile strength of 2.83 g/d and spun from a 98%DMTMC-2% TMC random copolymer) was cleaned by ultrasonic bath with 0.05%Triton X-100 water-ethanol solution. It was rinsed thoroughly indeionized water, and then with absolute alcohol. After air drying in alaminar flow hood, the yarn was coated with a 7% DMSO solution of 91%TMC-9% l-lactide random copolymer of MW˜87,000. The yarn was coated bydipping into the solution. After air drying (over 7 hrs.), it wasinverted and dip coated for a second time. Coating weight gain wasdetermined to be 6%. For insertion of the two ends of the prosthesisthrough the eye of the surgical needle, the ends were coated four moretimes with the solution so that the individual filaments cannot bereadily separated. After thorough air drying, the prosthesis was placedin a sterilization pack and sterilized with ethylene oxides. Theprothesis made was ready for rabbit Achilles tendon replacement.

C. Coated unaxial towed fiber devices

Similarly, a coated device of the 91% TMC 9% l-lactide coating a highstrength (extended chain) polyethylene fiber was constructed. A bundleof 14 Spectra 1000 medical grade extended chain polyethylene yarn (650denier yarn) was cleaned and dried as above. A 0.3% tetrahydrofuransolution of the 91% TMC-9% l-lactide copolymer was used for dip coating.Dip coating twice allowed a weight gain of 3% which was sufficient tohave most of the filaments adhere together but the prothesis was notcoated too heavily to become rigid and kink. The two ends were alsocoated extra for ready needle insertion. After air drying andsterilization with ethylene oxide, the prosthesis made was ready forreplacing the rabbit Achilles tendon.

D. Braided and crocheted fabric devices

Six yarns of twisted fibers are braided together to form a strand offabric 45 mm in length and with cross-sectional dimensions of 1 mm by 6mm. Similarly, yarns are crocheted into devices of variouscross-sectional diameter and length, depending on the end application.These fabrics are cleaned as discussed above and are to be used asreplacement devices for ligaments and tendons in small animals.

EXAMPLE 47 Wound Cover

Cloth type of materials made of the various bioresorbable fibers can beused. This includes woven and non-woven such as mesh, felt, cloth, knit,etc. After cleaning, adherence of these materials to a selective barrieris desirable. For example, a thin layer of medical-grade silicone filmcan be used.

Alternatively, an asymmetric membrane with one tight surface from thesebiopolymers may be used with or without such a barrier film.

EXAMPLE 48 Nerve Channel Implantation Studies

Mouse Sciatic Nerve Regeneration

Adult anesthetized C57BL/6J mouse with a sciatic nerve transected hadboth the proximal stump and distal stump secured by a single 10-0 nylonsuture and inserted into a 5-6 mm length of a nerve channel tube madefrom polytrimethylene carbonate (MW˜90,000) to give a final gap lengthof 3-4 mm. Postoperatively, at 6 weeks, the sciatic nerve of the animal,appropriately perfused for tissue studies, was again exposed andretransected 3 mm distal to the nerve guide tube. Nerve guides withenclosed regerated nerves were then dissected out, post-fixed in 2%osmium tetroxide and processed for plastic embedding (DER, Ted PellaInc.). Just before embedding, the tissue was usually divided intoseveral segments for sampling at multiple cross-section levels. For mostimplants, five levels were sampled by one micron sections. These levelswere: proximal sciatic stump at 1 to 2 mm proximal to the implant; threelevels (proximal, central, distal) within the tube through the originalgap, and the distal stump 1 to 2 mm distal to the implant. Data obtainedin the central section was used for comparison.

The results indicate that these channels do bioresorb and that they donot cause scar formation. They are as much or more vasotropic than thepoly d,l-lactide channels. In addition, the epineurium of theregenerated nerve using these nerve guides is much thinner than thatusing the lactide guides and approximates the size of the intact nerve.

EXAMPLE 49 Assymmetric Membrance From Block Copolymer

An ABA block copolymer was used to prepare the asymmetric membrane; theB block was 1:1 dimethyltrimethylene carbonate (DMTMC):trimethylenecarbonate (TMC), the A block was DMTMC homopolymer, and the A:B ratiowas 70:30. The weight average (MW) was about 180,000. A sample of thepolymer (5 g) was dissolved in a mixture of tetrahydrofuran (35 mL) anddiglyme (5 mL) and protected from drafts. The solvents were allowed toevaporate for about 4 hrs, then the plate was placed in an oven at45°-50° C. overnight. The resulting film was removed from the plate andsubmitted for analysis by scanning electron microscopy. This showed thatthe film has a tight, smooth, non-porous side (the glass side), and ahighly porous reverse side. Cross section of the film shows that thereare many pores and channels thoroughout the bulk of the film except forthe side of the tight skin. Films varying in thickness from about 80 toabout 350 μm were prepared in this way.

EXAMPLE 50 Fabrication of Rod and Ribbon as Internal Support inConjunction with Balloon Angioplasty

An ABA block copolymer [A:B=80:20, A=DMTMC, B=1:9=DMTMC:TMC] wasextruded at 190° C. in the modified Instron extruder, with either around or a rectangular die. The rod or ribbon produced was stored in aClass 100 laminar flow hood for 48 hrs., before it was cold drawn togive an overall draw ratio of eight and six repectively. The product waswrapped around a 2 mm diameter glass rod as mandrel, in a spiralfashion, and stabilized at both ends. Dimethyl sulfoxide was addeddropwise to the "spiral" while the mandrel was rotating at 5 RPM by amotor in a horizontal position. After seven days, the product wasremoved from the mandrel. The spiral form of the product was retained.This type of completely bioresorbable "spring" can be used inconjunction with balloon angioplasty to help to maintain the patency ofre-opened blood vessel, replacing clips or springs made of stainlesssteel or other materials.

EXAMPLE 51

Sample 2 from Example 28 was an ABA block copolymer with A:B ratio of30:70 and with 1-LA (A block) and a 9 and 1 copolymer of TMC and d,1-LA(B block). Elastic tubes, useful as nerve channels, fallopian tubereplacements, were extruded at 200° C. similar to Example 41. Whenever,the tubes were deliberately pinched close, they would reopenimmediately. Tube inner diameters of 0.5 to 3 mm were achieved.

EXAMPLE 52 Biopolymer Coated Polyurethane Devices

ComfaDerm KM-1422-00 (obtained from Semex Medical, Malvern, Pa.,U.S.A.), a medical grade foamed, flexible polyurethane coated on oneside with a pressure sensitive medical adhesive, was coated from theother side with a 4% DMSO solution of 90% TMC/10% 1-lactide randomcopolymer. Once the solution was applied evenly on the surface andsubjected to 110° C. heating in an air oven, the solution soaked throughthe foam and, therefore coated the system, in a matter of minutes.Thorough drying for over 12 hrs afforded an evenly coated flexiblefoamed polyurethane based device.

Similarly, dimethylacetamide solution casted thin or thick films ofpolyurethane, e.g., Pellethane 2103-80AE and Pellethane X0119-70A(obtained from Upjohn Co.), were readily coated with a 4% DMSObiopolymer coating solution. Once the casted polyurethane film iscasted, dried in an 120° C. oven, the DMSO coating solution was addedonto the film while still hot. The solution had a tendancy to adhereunevenly; however, with care in spreading the solution, and subjectingthe system to heating in the oven, and repeating the spreading andheating cycle a few times over time, e.g., one hour, even coatedsurfaces were obtained. Strong adhesion was achieved as demonstrated bypin pricking and rubbing, which did not separate the two films.

EXAMPLE 53 Trimethylene Carbonate/1-Lactide [90/ ] Random Copolymer

In a 100 mL reaction flask fitted with mechancial stirrer and argoninlet were combined trimethylene carbonate (51.45 g, 504 mmol),1-lactide (8.07 g, 56 mmol), and 1,6-hexanediol (47 mg, 0.40 mmol). Theflask was evacuated and filled with argon several times, immersed in anoil bath at 160° C. and stirring was initiated. After 10 mins., thepolymerization catalyst, 25 μL of 0.20M solution of tin(II) octoate intoluene, was added via syringe. The mixture was stirred at 160° C. for 4hrs., then the polymer was removed from the flask, dissolved intetrahydrofuran (450 mL), and precipitated into methanol (1200 mL) in ablender. The precipitated polymer was stirred with additional methanol(400 mL) in the blender, filtered, and dried in the vacuum oven at 50°C. Yield: 43.8 g (74%). Weight average molecular weight=120,000(polydispersity 1.5). Proton NMR (400 MHz) shows a final composition of80% trimethylene carbonate units and 20% lactic acid units (theoretical82% and 18%, respectively). This polymer is especially useful as acoating polymer.

What is claimed is:
 1. A random copolymer comprising at least one typeof recurring monomeric unit of the following General Structures I andII: ##STR11## wherein: Z is --C(R₅ R₆)--, --NR₅ --, --O-- or acombination thereof, where Z is selected such that there are no adjacentheteroatoms;n is from 1 to about 8; m is from 1 to about 8; R₁, R₂, R₃,and R₄ are the same or different at each occurrence and are hydrogen,aryloxyalkyl, alkyoxyaryl, aryloxyaryl, arylalkyl, alkylarylalkyl,arylalkylaryl, alkylaryl, arylcarbonylalkyl, alkyl, aryl,alkylcarbonyalkyl, cycloalkyl, arylcarbonylaryl, alkylcarbonylarly,alkoxyalkyl, or aryl or alkyl substituted with one or more biologicallycompatible substituents; and R₅ and R₆ are the same or different and areR₁, R₂, R₃, R₄, dialkylamino, diarylamino, alkylarylamino, alkoxy,aryloxy, alkanoyl, or arylcarbonyl, or any two of R₁ to R₆ together mayform an alkylene chain completing a 3, 4, 5, 6, 7, 8 or 9 memberedalicyclic fused, spiro, bicyclic or tricyclic ring system or acombination thereof, which system may optionally include one or morenon-adjacent carbonyl, oxa, alkylaza or arylaza groups; With the provisothat when said copolymers have recurring units of the Structure Iderived from trimethylene carbonate, the other recurring monomeric unitsof copolymer are not derived from gylcolide or glycolic acid.
 2. Therandom copolymer of claim 1 wherein R₁, R₂, R₃, R₄, R₅, and R₆ are thesame or different and are selected from the groups consisting ofhydrogen, alkyl, cycloalkyl, alkylphenyl, alkoxyalkyl and phenylalkyl,and phenyl, alkylphenyl and phenylalkyl substituted with one or morealkyl or alkoxy groups.
 3. The random polymer of claim 2 wherein:Z is--C(R₅ R₆)--, --O-- or a combination thereof; n is 1, 2, or 3; m is 1,2, 3, 4, 5 or 6; and R₁ to R₆ are selected from the group consisting ofsubstituents in which aliphatic moieties include up to about 10 carbonatoms and aryl moieties include up to about 16 carbon atoms.
 4. Therandom copolymer of claim 1 comprising at least one type of recurringmonomeric unit of the following general Structures II and III: ##STR12##wherein: n is 1 to about 3;m is 1 to about 4; R₁, R₂, R₃, R₄, R₅, and R₆are the same or different and are hydrogen, aryl, alkylaryl, arylalkylor alkyl, or R₅ and R₆ together may form an aliphatic chain having fromabout 3 to about 10 membered spiro, bicyclic or tricyclic ring structureor a combination thereof.
 5. The block copolymer of claim 4 wherein:n is1, 2 or 3; m is 1, 2 or 3; and R₁, R₂, R₃, R₄, R₅ and R₆ are the same ordifferent and are hydrogen, alkyl, phenylalkyl or alkylphenyl.
 6. Theblock copolymer of claim 5 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are thesame or different and are hydrogen or alkyl having from 1 to about 7carbon atoms.
 7. The random copolymer of claim 6 comprising at least onetype of recurring monomeric unit of the following Structure III:##STR13##
 8. The random copolymer of claim 7 wherein R₅ and R₆ are thesame or different and are hydrogen or alkyl having from 1 to about 4carbon atoms.
 9. The random copolymer of claim 1 wherein the wt % ofrecurring monomeric units of the Structure I or Structure II included insaid copolymer is at least about 50 wt % based on the total weight ofmonomeric units in the copolymer.
 10. The random copolymer of claim 9wherein said wt % is from about 80 wt % to about 100 wt %.
 11. Therandom copolymer of claim 10 wherein said wt % is from about 85 to about99 wt %.
 12. The random copolymer of claim 1 wherein said copolymercomprises at least one type of recurring unit of the General StructuresI and II, and at least one other type of recurring monomeric unitderived from the group consisting of substituted carbonates,non-substituted carbonates, lactones, dioxepanones, dioxanones otherthan carbonates, epoxides, epoxide/CO₂, anhydrides, orthoesters, andorthocarbonates.
 13. The random copolymer of claim 12 wherein saidcopolymer comprises recurring monomeric units derived from2,2-dimethyltrimethylene carbonate and at least one other type ofrecurring monomeric unit derived from orthocarbonates, orthoesters,lactones, trimethylene carbonates, ethylene carbonates or tetramethylenecarbonates.
 14. The random copolymer of claim 13 wherein said copolymercomprises recurring monomeric units derived from trimethylene carbonateand recurring monomeric units derived from lactones.
 15. The copolymerof claim 1 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same or differentand are selected from the group consisting of hydrogen, alkyl,cycloalkyl, alkylaryl, alkoxyalkyl, aryloxyalkyl, arloxyaryl, aryl andarylalkyl groups, and aryl, arylalkyl or alkylaryl substituted with oneor more alkyl, alkoxy and alkoxyalkyl groups.
 16. The copolymer of claim15 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and areselected from the groups consisting of hydrogen, alkyl, cycloalkyl,alkylphenyl, alkoxyalkyl and phenylakyl, and phenyl, alkylphenyl andphenylalkyl substituted with one or more alkyl or alkoxy groups.
 17. Thecopolymer of claim 16 wherein:Z is --C(R₅ R₆)--, --O-- or a combinationthereof; n is 1, 2, or 3; m is 1, 2, 3, 4, 5 or 6; and R₁ to R₆ areselected from the group consisting of substitutents in which aliphaticmoieties include up to about 10 carbon atoms and aryl moieties includeup to about 16 carbon atoms.
 18. The copolymer of claim 15 wherein:n is1, 2 or 3; m is 1, 2 or 3; and R₁, R₂, R₃, R₄, R₅ and R₆ are the same ordifferent and are hydrogen, alkyl, phenylalkyl or alkylphenyl.
 19. Thecopolymer of claim 18 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same ordifferent and are hydrogen or alkyl having from 1 to about 7 carbonatoms.
 20. The copolymer of claim 1 wherein said biopolymers comprisesat least one type of recurring monomeric unit moieties selected from thegroup consisting of: ##STR14## wherein: R₅ and R₆ are the same ordifferent and are hydrogen, alkyl, aryl, cycloalkyl, arylalkyl,alkoxyalkyl, aryloxyalkyl, or aryl or arylalkyl substituted with one ormore alkyl, alkoxy, alkanoyl, or dialkylamino groups, or R₅ and R₆together may form an alkylene chain completing a 4, 5, 5, 7, 8, 9 or 10membered spiro, bicyclic or tricyclic ring structure or a combinationthereof, which structure may optionally include one or more non-adjacentdivalent carbonyl, oxa, alkylaza or arylaza groups, with the provisothat at least one or R₅ or R₆ is other than hydrogen; andn is 1, 2 or 3.21. The copolymer of claim 20 selected from the group consisting ofpoly(trimethylene carbonate-co-lactide), poly(dimethyltrimethylenecarbonate-co-trimethylene carbonate) and poly(dimethyltrimethylenecarbonate-co-caprolactone).
 22. The copolymer poly(trimethylenecarbonate-co-lactide).
 23. The copolymer poly(dimethyltrimethylenecarbonate-co-trimethylene carbonate).
 24. The copolymer of claim 22wherein the weight ratio of dimethyltrimethylene carbonate totrimethylene carbonate in said poly(dimethyltrimethylenecarbonate-co-trimethylene carbonate) is from about 25 to 75 to about97:5 to 2.5.
 25. The copolymer of claim 24 wherein said weight ration isfrom about 56 to 44 to about 97:5 to 2.5.
 26. The copolymer of claim 25wherein said weight ratio is from about 79 to 21 to about 97.5 to 2.5.27. The copolymer of claim 26 wherein said weight ratio is from about 95to 5 to about 97.5 to 2.5.
 28. The copolymer of claim 20 wherein R₅ andR₆ are the same or different and are phenyl, phenylalkyl, alkylphenyl,alkyl, or R₅ and R₆ together form alkylene a divalent chain forming a 4to 8 membered ring structure.
 29. The copolymer of claim 28 wherein R₅and R₆ together form a 5 to 7 membered spiro, or bicyclic ring structureor a combination thereof.
 30. The copolymer of claim 20 wherein R₅ andR₆ are the same.
 31. The copolymer of claim 30 wherein R₅ and R₆ are thesame or different and are alkyl, phenyl, alkylphenyl or phenylalkyl. 32.The copolymer of claim 20 wherein R₅ and R₆ are hydrogen.
 33. Thecopolymer of claim 31 wherein R₅ and R₆ are the same or different andare alkyl of from about 1 to 7 carbon atoms.
 34. The copolymer of claim33 wherein R₅ and R₆ are alkyl of about 1 to 4 carbon atoms.
 35. Thecopolymer of claim 1 wherein the wt % of recurring monomeric units ofthe Structure I or Structure II included in said copolymer is at leastabout 50 wt % based on the total wt of monomeric units in the copolymer.36. The copolymer of claim 35 wherein said wt % is from about 80 wt % toabout 100 wt %.
 37. The copolymer of claim 36 wherein said wt % is fromabout 85 to about 100 wt %.
 38. The copolymer of claim 37 wherein saidwt % is from about 85 to about 99 wt %.
 39. The copolymer of claim 1wherein said biopolymers are selected from the group consisting ofrandom copolymers comprising at least one type of recurring unit of theGeneral Structures I and II, and at least other type of recurringmonomeric units derived from the group consisting of substitutedcarbonates, non-substituted carbonates, lactones, dioxepanones,dioxanones other than carbonates, epoxides, epoxide/CO₂, anhydrides,orthoesters, and orthocarbonates.
 40. The copolymer of claim 1 whereinsaid copolymer comprises recurring monomeric units derived from2,2-dimethyltrimethylene carbonate and other types of recurringmonomeric units derived from orthocarbonates, orthoesters, lactones,trimethylene carbonates, ethylene carbonates and tetramethylenecarbonates.
 41. The copolymer of claim 1 wherein said copolymercomprises recurring monomeric units derived from trimethylene carbonateand other types of recurring monomeric units derived from lactones. 42.The device of claim 1 which is a totally or partially bioresorbablemedical device suitable for implantation in side of a living system topromote regeneration of body tissue.
 43. The device of claim 1 whichfurther comprises a biodurable portion.